共查询到20条相似文献,搜索用时 31 毫秒
1.
Daniel H?nggi Jason Perrin Sven Eicker Kerim Beseoglu Nima Etminan Marcel Alexander Kamp Hi-Jae Heiroth Nadia Bege Stephan Macht Katrin Frauenknecht Clemens Sommer Thomas Kissel Hans-Jakob Steiger 《PloS one》2012,7(9)
Background and Purpose
To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH).Methods
70 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and the 3) treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40%) of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA). Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry.Results
DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only), as compared to the sham operated group (p<0.001). Only animals within group 3 and the highest nimodipine microparticles concentration (40%) as well as group 1 (sham) demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury.Conclusions
Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity. 相似文献2.
Background
The dystrophin gene, which is mutated in Duchenne muscular dystrophy (DMD), encodes a large cytoskeletal protein present in muscle fibers. While dystrophin in skeletal muscle has been extensively studied, the function of dystrophin in vascular smooth muscle is less clear. Here, we have analyzed the role of dystrophin in injury-induced arterial neointima formation.Methodology/Principal Findings
We detected a down-regulation of dystrophin, dystroglycan and β-sarcoglycan mRNA expression when vascular smooth muscle cells de-differentiate in vitro. To further mimic development of intimal lesions, we performed a collar-induced injury of the carotid artery in the mdx mouse, a model for DMD. As compared with control mice, mdx mice develop larger lesions with increased numbers of proliferating cells. In vitro experiments demonstrate increased migration of vascular smooth muscle cells from mdx mice whereas the rate of proliferation was similar in cells isolated from wild-type and mdx mice.Conclusions/Significance
These results show that dystrophin deficiency stimulates neointima formation and suggest that expression of dystrophin in vascular smooth muscle cells may protect the artery wall against injury-induced intimal thickening. 相似文献3.
Fan Yang Jian F. Zhao Qi Y. Shou Xiao J. Huang Gang Chen Ke B. Yang Shi G. Zhang Bo D. Lv Hui Y. Fu 《PloS one》2014,9(8)
Background
Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis.Aim
We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats.Methods
Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM).Results
Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats.Conclusions
CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury–induced ED. 相似文献4.
Objective
To investigate a novel method, namely using bilateral internal iliac artery ligation combined with a high-fat diet (BCH), for establishing a rat model of erectile dysfunction (ED) that, compared to classical approaches, more closely mimics the chronic pathophysiology of human ED after acute ischemic insult.Materials and Methods
Forty 4-month-old male Sprague Dawley rats were randomly placed into five groups (n = 8 per group): normal control (NC), bilateral internal iliac artery ligation (BIIAL), high-fat diet (HFD), BCH, and mock surgery (MS). All rats were induced for 12 weeks. Copulatory behavior, intracavernosal pressure (ICP), ICP/mean arterial pressure, hematoxylin-eosin staining, Masson''s trichrome staining, serum lipid levels, and endothelial and neuronal nitric oxide synthase immunohistochemical staining of the cavernous smooth muscle and endothelium were assessed. Data were analyzed by SAS 8.0 for Windows.Results
Serum total cholesterol and triglyceride levels were significantly higher in the HFD and BCH groups than the NC and MS groups. High density lipoprotein levels were significantly lower in the HFD and BCH groups than the NC and MS groups. The ICP values and mount and intromission numbers were significantly lower in the BIIAL, HFD, and BCH groups than in the NC and MS groups. ICP was significantly lower in the BCH group than in the BIIAL and HFD groups. Cavernous smooth muscle and endothelial damage increased in the HFD and BCH groups. Cavernous smooth muscle to collagen ratio, nNOS and eNOS staining decreased significantly in the BIIAL, HFD, and BCH groups compared to the NC and MS groups.Conclusions
The novel BCH model mimics the chronic pathophysiology of ED in humans and avoids the drawbacks of traditional ED models. 相似文献5.
Background
The goal of this study was to evaluate the efficacy of a nanoporous CREG-eluting stent (CREGES) in inhibiting neointimal formation in a porcine coronary model.Methods
In vitro proliferation assays were performed using isolated human endothelial and smooth muscle cells to investigate the cell-specific pharmacokinetic effects of CREG and sirolimus. We implanted CREGES, control sirolimus-eluting stents (SES) or bare metal stents (BMS) into pig coronary arteries. Histology and immunohistochemistry were performed to assess the efficacy of CREGES in inhibiting neointimal formation.Results
CREG and sirolimus inhibited in vitro vascular smooth muscle cell proliferation to a similar degree. Interestingly, human endothelial cell proliferation was only significantly inhibited by sirolimus and was increased by CREG. CREGES attenuated neointimal formation after 4 weeks in porcine coronary model compared with BMS. No differences were found in the injury and inflammation scores among the groups. Scanning electron microscopy and CD31 staining by immunohistochemistry demonstrated an accelerated reendothelialization in the CREGES group compared with the SES or BMS control groups.Conclusions
The current study suggests that CREGES reduces neointimal formation, promotes reendothelialization in porcine coronary stent model. 相似文献6.
Yuan Hong AnWen Shao Jianfeng Wang Sheng Chen HaiJian Wu Devin W. McBride Qun Wu XueJun Sun JianMin Zhang 《PloS one》2014,9(4)
Backgrounds
Early brain injury (EBI) plays a key role in the pathogenesis of subarachnoid hemorrhage (SAH). Neuronal apoptosis is involved in the pathological process of EBI. Hydrogen can inhibit neuronal apoptosis and attenuate EBI following SAH. However, the molecular mechanism underlying hydrogen-mediated anti-apoptotic effects in SAH has not been elucidated. In the present study, we aimed to evaluate whether hydrogen alleviates EBI after SAH, specifically neuronal apoptosis, partially via the Akt/GSK3β signaling pathway.Methods
Sprague-Dawley rats (n = 85) were randomly divided into the following groups: sham group (n = 17), SAH group (n = 17), SAH + saline group (n = 17), SAH + hydrogen-rich saline (HS) group (n = 17) and SAH + HS + (n = 17) group. HS or an equal volume of physiological saline was administered immediately after surgery and repeated 8 hours later. The PI3K inhibitor, Ly294002, was applied to manipulate the proposed pathway. Neurological score and SAH grade were assessed at 24 hours after SAH. Western blot was used for the quantification of Akt, pAkt, GSK3β, pGSK3β, Bcl-2, Bax and cleaved caspase-3 proteins. Neuronal apoptosis was identified by double staining of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining and NeuN, and quantified by apoptosis index. Immunohistochemistry and immunofluorescent double-labeling staining was performed to clarify the relationships between neuronal apoptosis and pAkt or pGSK3β. Ly294002Results
HS significantly reduced neuronal apoptosis and improved neurological function at 24 hours after SAH. The levels of pAkt and pGSK3β, mainly expressed in neurons, were markedly up-regulated. Additionally, Bcl-2 was significantly increased while Bax and cleaved caspase-3 was decreased by HS treatment. Double staining of pAkt and TUNEL showed few colocalization of pAkt-positive cells and TUNEL-positive cells. The inhibitor of PI3K, , suppressed the beneficial effects of HS. Ly294002Conclusions
HS could attenuate neuronal apoptosis in EBI and improve the neurofunctional outcome after SAH, partially via the Akt/GSK3β pathway. 相似文献7.
Christian S. Bruells Ingmar Bergs Rolf Rossaint Jun Du Christian Bleilevens Andreas Goetzenich Joachim Weis Michael P. Wiggs Scott K. Powers Marc Hein 《PloS one》2014,9(1)
Background
Mechanical ventilation (MV) induces diaphragmatic muscle fiber atrophy and contractile dysfunction (ventilator induced diaphragmatic dysfunction, VIDD). It is unknown how rapidly diaphragm muscle recovers from VIDD once spontaneous breathing is restored. We hypothesized that following extubation, the return to voluntary breathing would restore diaphragm muscle fiber size and contractile function using an established rodent model.Methods
Following 12 hours of MV, animals were either euthanized or, after full wake up, extubated and returned to voluntary breathing for 12 hours or 24 hours. Acutely euthanized animals served as controls (each n = 8/group). Diaphragmatic contractility, fiber size, protease activation, and biomarkers of oxidative damage in the diaphragm were assessed.Results
12 hours of MV induced VIDD. Compared to controls diaphragm contractility remained significantly depressed at 12 h after extubation but rebounded at 24 h to near control levels. Diaphragmatic levels of oxidized proteins were significantly elevated after MV (p = 0.002) and normalized at 24 hours after extubation.Conclusions
These findings indicate that diaphragm recovery from VIDD, as indexed by fiber size and contractile properties, returns to near control levels within 24 hours after returning to spontaneous breathing. Besides the down-regulation of proteolytic pathways and oxidative stress at 24 hours after extubation further repairing mechanisms have to be determined. 相似文献8.
Xue Zhang Daniel G. Woolley Stephan P. Swinnen Hilde Feys Raf Meesen Nicole Wenderoth 《PloS one》2014,9(7)
Objective
Previous studies have investigated how tDCS over the primary motor cortex modulates excitability in the intrinsic hand muscles. Here, we tested if tDCS changes corticomotor excitability and/or cortical inhibition when measured in the extensor carpi radialis (ECR) and if these aftereffects can be successfully assessed during controlled muscle contraction.Methods
We implemented a double blind cross-over design in which participants (n = 16) completed two sessions where the aftereffects of 20 min of 1 mA (0.04 mA/cm2) anodal vs sham tDCS were tested in a resting muscle, and two more sessions where the aftereffects of anodal vs sham tDCS were tested in an active muscle.Results
Anodal tDCS increased corticomotor excitability in ECR when aftereffects were measured with a low-level controlled muscle contraction. Furthermore, anodal tDCS decreased short interval intracortical inhibition but only when measured at rest and after non-responders (n = 2) were removed. We found no changes in the cortical silent period.Conclusion
These findings suggest that targeting more proximal muscles in the upper limb with anodal tDCS is achievable and corticomotor excitability can be assessed in the presence of a low-level controlled contraction of the target muscle. 相似文献9.
Anne Holt Müller Gro Klitgaard Povlsen Claus Heiner Bang-Berthelsen Lars Schack Kruse Janne Nielsen Karin Warfvinge Lars Edvinsson 《BMC genomics》2015,16(1)
Background
microRNAs (miRNAs) are important regulators of translation and have been implicated in the pathogenesis of a number of cardiovascular diseases, including stroke, and suggested as possible prognostic biomarkers. Our aim was to identify miRNAs that are differentially regulated in cerebral arteries after subarachnoid hemorrhage (SAH), using a rat injection model of SAH and a qPCR-based screen of 728 rat miRNAs. Additionally, serum was analyzed for a possible spill-over to the circulation of regulated miRNAs from the vessel walls.Results
We identified 482 different miRNAs expressed in cerebral arteries post-SAH. Two miRNAs, miR-30a and miR-143, were significantly upregulated in cerebral arteries after SAH when compared to sham-operated animals. However, none of these exhibited significantly altered serum levels after SAH versus post-sham surgery. The most robust upregulation was seen for miR-143, which has several predicted targets and is a strong regulator of vascular morphology. We hypothesize that miR-30a and miR-143 may play a role in the vascular wall changes seen after SAH.Conclusions
We report that miR-30a and miR-143 in the cerebral arteries show significant changes over time after SAH, but do not differ from sham-operated rats at 24 h post-SAH. Although this finding suggests interesting novel possible mechanisms involved in post-SAH cerebrovascular changes, the lack of regulation of these miRNAs in serum excludes their use as blood-borne biomarkers for cerebrovascular changes following SAH.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1341-7) contains supplementary material, which is available to authorized users. 相似文献10.
Background
Asthma is a chronic disease that is characterized by airway hyperresponsiveness and airway remodeling. The underlying mechanisms that mediate the pathological processes are not fully understood. Abl is a non-receptor protein tyrosine kinase that has a role in the regulation of smooth muscle contraction and smooth muscle cell proliferation in vitro. The role of Abl in airway hyperresponsiveness and airway remodeling in vivo is largely unknown.Methods
To evaluate the role of Abl in asthma pathology, we assessed the expression of Abl in airway tissues from the ovalbumin sensitized and challenged mouse model, and human asthmatic airway smooth muscle cells. In addition, we generated conditional knockout mice in which Abl expression in smooth muscle was disrupted, and then evaluated the effects of Abl conditional knockout on airway resistance, smooth muscle mass, cell proliferation, IL-13 and CCL2 in the mouse model of asthma. Furthermore, we determined the effects of the Abl pharmacological inhibitors imatinib and GNF-5 on these processes in the animal model of asthma.Results
The expression of Abl was upregulated in airway tissues of the animal model of asthma and in airway smooth muscle cells of patients with severe asthma. Conditional knockout of Abl attenuated airway resistance, smooth muscle mass and staining of proliferating cell nuclear antigen in the airway of mice sensitized and challenged with ovalbumin. Interestingly, conditional knockout of Abl did not affect the levels of IL-13 and CCL2 in bronchoalveolar lavage fluid of animals treated with ovalbumin. However, treatment with imatinib and GNF-5 inhibited the ovalbumin-induced increase in IL-13 and CCL2 as well as airway resistance and smooth muscle growth in animals.Conclusions
These results suggest that the altered expression of Abl in airway smooth muscle may play a critical role in the development of airway hyperresponsiveness and airway remodeling in asthma. Our findings support the concept that Abl may be a novel target for the development of new therapy to treat asthma. 相似文献11.
Background
Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis or occlusion of the terminal portion of internal carotid arteries and the formation of a vascular network at the base of the brain. The pathogenesis of MMD is still unclear.Methodology/Principal Findings
We retrospectively analyzed clinical data for 65 consecutive patients with MMD in our institutions and evaluated the histopathological and immunohistochemical findings of intracranial vessels from 3 patients. The onset age distribution was found to have 1 peak at 40–49 year-old age group, no significant difference was observed in the female-to-male ratio (F/M = 1.2). Intracranial hemorrhage was the predominant disease type (75%). Positive family history was observed in 4.6% of patients. Histopathological findings were a narrowed lumen due to intimal fibrous thickening without significant inflammatory cell infiltration, and the internal elastic lamina was markedly tortuous and stratified. All 3 autopsy cases showed vacuolar degeneration in the cerebrovascular smooth muscle cells. Immunohistochemical study showed the migration of smooth muscle cells in the thickened intima, and aberrant expression of IgG and S100A4 protein in vascular smooth muscle cells. The Complement C3 immunoreactivity was negative.Conclusion/Significance
This study indicated that aberrant expression of IgG and S100A4 protein in intracranial vascular wall of MMD patients, which suggested that immune-related factors may be involved in the functional and morphological changes of smooth muscle cells, and finally caused the thickened intima. A possible mechanism is that deposits of IgG in the damaged internal elastic lamina may underlie the disruption of internal elastic lamina, which facilitated S100A4 positive SMCs migrated into intima through broken portions of the internal elastic lamina, resulting in lumen stenosis or occlusion, leading to compensatory small vessels proliferation. 相似文献12.
Marian Christoph Neidert Michael Sprenger Heini Wernli Jan-Karl Burkhardt Niklaus Krayenbühl Oliver Bozinov Luca Regli Christoph Michael Woernle 《PloS one》2013,8(12)
Objective
To assess the potential meteorological influence on the incidence of aneurysmal subarachnoid hemorrhage (SAH). Previous studies used inhomogeneous patient groups, insufficient study periods or inappropriate statistics.Patients and Methods
We analyzed 511 SAH admissions between 2004 and 2012 for which aneurysmal rupture occurred within the Zurich region. The hourly meteorological parameters considered are: surface pressure, 2-m temperature, relative humidity and wind gusts, sunshine, and precipitation. For all parameters we investigate three complementary statistical measures: i) the time evolution from 5 days before to 5 days after the SAH occurrence; ii) the deviation from the 10-year monthly mean; and iii) the change relative to the parameter''s value two days before SAH occurrence. The statistical significance of the results is determined using a Monte Carlo simulation combined with a re-sampling technique (1000×).Results
Regarding the meteorological parameters considered, no statistically significant signal could be found. The distributions of deviations relative to the climatology and of the changes during the two days prior to SAH events agree with the distributions for the randomly chosen days. The analysis was repeated separately for winter and summer to exclude compensating effects between the seasons.Conclusion
By using high-quality meteorological data analyzed with a sophisticated and robust statistical method no clearly identifiable meteorological influence for the SAH events considered can be found. Further studies on the influence of the investigated parameters on SAH incidence seem redundant. 相似文献13.
Jing Zhang Jing Chen Jian Yang Changwu Xu Jiawang Ding Jun Yang Qing Guo Qi Hu Hong Jiang 《PloS one》2014,9(1)
Background/Aim
Neointimal formation after vessel injury is a complex process involving multiple cellular and molecular processes. Inhibition of intimal hyperplasia plays an important role in preventing proliferative vascular diseases, such as restenosis. In this study, we intended to identify whether sodium ferulate could inhibit neointimal formation and further explore potential mechanisms involved.Methods
Cultured vascular smooth muscle cells (VSMCs) isolated from rat thoracic aorta were pre-treated with 200 µmol/L sodium ferulate for 1 hour and then stimulated with 1 µmol/L angiotensin II (Ang II) for 1 hour or 10% serum for 48 hours. Male Sprague-Dawley rats subjected to balloon catheter insertion were administrated with 200 mg/kg sodium ferulate (or saline) for 7 days before sacrificed.Results
In presence of sodium ferulate, VSMCs exhibited decreased proliferation and migration, suppressed intracellular reactive oxidative species production and NADPH oxidase activity, increased SOD activation and down-regulated p38 phosphorylation compared to Ang II-stimulated alone. Meanwhile, VSMCs treated with sodium ferulate showed significantly increased protein expression of smooth muscle α-actin and smooth muscle myosin heavy chain protein. The components of Notch pathway, including nuclear Notch-1 protein, Jagged-1, Hey-1 and Hey-2 mRNA, as well as total β-catenin protein and Cyclin D1 mRNA of Wnt signaling, were all significantly decreased by sodium ferulate in cells under serum stimulation. The levels of serum 8-iso-PGF2α and arterial collagen formation in vessel wall were decreased, while the expression of contractile markers was increased in sodium ferulate treated rats. A decline of neointimal area, as well as lower ratio of intimal to medial area was observed in sodium ferulate group.Conclusion
Sodium ferulate attenuated neointimal hyperplasia through suppressing oxidative stress and phenotypic switching of VSMCs. 相似文献14.
Marlene Fischer Anelia Dietmann Ronny Beer Gregor Broessner Raimund Helbok Bettina Pfausler Erich Schmutzhard Peter Lackner 《PloS one》2013,8(3)
Background
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are involved in vascular remodeling, (neuro)inflammation, blood-brain barrier breakdown and neuronal apoptosis. Proinflammatory mechanisms are suggested to play an important role during early brain injury and cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). This study aimed to analyze MMP-3, MMP-9, TIMP-1 and TIMP-3 in patients with SAH and their respective association with cerebral vasospasm (CVS).Methods
Blood samples were collected in 20 SAH patients on days 1 to 7, 9, 11, 13 and 15 and 20 healthy age and gender matched volunteers. Serum MMPs and TIMPs were analyzed using enzyme-linked immunosorbent assay. Doppler sonographic CVS was defined as a mean blood flow velocity above 120 cm/sec in the middle cerebral artery. When discharged from hospital and at 6 month follow-up neurological outcome was evaluated using the Glasgow Outcome Score and the modified Rankin Scale.Results
MMP-9 was higher in SAH patients compared to healthy controls (p<0.001). Patients with CVS (n = 11) had elevated MMP-9 serum levels compared to patients without CVS (n = 9, p<0.05). Higher MMP-9 was observed in the presence of cerebral ischemia associated with cerebral vasospasm (p<0.05). TIMP-1 was increased in patients with SAH on day 4 (p<0.05). There was an imbalance of the MMP-9/TIMP-1 ratio in favor of MMP-9 in SAH patients, in particular those with CVS (p<0.001). MMP-3 and TIMP-3 were significantly lower in SAH patients throughout day 4 and day 7, respectively (p<0.05). We did not find an association between MMP-, TIMP levels and neurological outcome after 6 months.Conclusions
MMP-3 and -9 are differentially regulated in SAH patients with both enzymes showing peak levels correlating with the development of CVS. The inhibitors TIMP-1 and -3 were low during the acute phase after SAH and increased later on which might suggest a preponderance of pro-inflammatory mechanisms. 相似文献15.
Habibollah Saadat Seyed Ali Ziai Maryam Ghanemnia Mohammad Hasan Namazi Morteza Safi Hosein Vakili Ali Dabbagh Omid Gholami 《PloS one》2012,7(9)
Background
There is evidence that opium addiction has immunosuppressant effects. Coronary artery disease (CAD) is a condition resulted from atherosclerosis which is dependent on the immune response.Purpose
To evaluate plasma levels of interleukin-6 and interleukin-1Ra in 30 patients with three-vessel coronary artery disease, ejection fraction of more than 35% and to evaluate their changes after prognostic treadmill test in 15 opium addicted and 15 non-addicted patients.Methods
The participants underwent prognostic treadmill test and plasma levels of interleukin-6 (IL-6) and interleukin-1Ra (IL-1Ra) were evaluated with ELISA method before, just after and 4 hours after the test.Results
IL-1Ra (2183 pg/ml) tended to decrease over time in the opium addicted group (1372 pg/ml after prognostic treadmill test and 1034 pg/ml 4 hours after that), although such decrease did not reach the statistical significance. IL-1Ra levels were significantly higher in opium addicted than in non addicted patients. Opium addiction had no significant effect on IL-6 changes.Conclusion
Consumption of opium in CAD patients is associated with higher IL-1Ra levels. 相似文献16.
Javier Moral-Sanz Carmen Menendez Laura Moreno Enrique Moreno Angel Cogolludo Francisco Perez-Vizcaino 《Respiratory research》2011,12(1):51
Background
Insulin resistance and obesity are strongly associated with systemic cardiovascular diseases. Recent reports have also suggested a link between insulin resistance with pulmonary arterial hypertension. The aim of this study was to analyze pulmonary vascular function in the insulin resistant obese Zucker rat.Methods
Large and small pulmonary arteries from obese Zucker rat and their lean counterparts were mounted for isometric tension recording. mRNA and protein expression was measured by RT-PCR or Western blot, respectively. KV currents were recorded in isolated pulmonary artery smooth muscle cells using the patch clamp technique.Results
Right ventricular wall thickness was similar in obese and lean Zucker rats. Lung BMPR2, KV1.5 and 5-HT2A receptor mRNA and protein expression and KV current density were also similar in the two rat strains. In conductance and resistance pulmonary arteries, the similar relaxant responses to acetylcholine and nitroprusside and unchanged lung eNOS expression revealed a preserved endothelial function. However, in resistance (but not in conductance) pulmonary arteries from obese rats a reduced response to several vasoconstrictor agents (hypoxia, phenylephrine and 5-HT) was observed. The hyporesponsiveness to vasoconstrictors was reversed by L-NAME and prevented by the iNOS inhibitor 1400W.Conclusions
In contrast to rat models of type 1 diabetes or other mice models of insulin resistance, the obese Zucker rats did not show any of the characteristic features of pulmonary hypertension but rather a reduced vasoconstrictor response which could be prevented by inhibition of iNOS. 相似文献17.
Zuzanna Rowinska Simone Gorressen Marc W. Merx Thomas A. Koeppel Elisa A. Liehn Alma Zernecke 《PloS one》2014,9(7)
Introduction
The aim of our study was to develop a reproducible murine model of elastase-induced aneurysm formation combined with aortic transplantation.Methods
Adult male mice (n = 6–9 per group) underwent infrarenal, orthotopic transplantation of the aorta treated with elastase or left untreated. Subsequently, both groups of mice were monitored by ultrasound until 7 weeks after grafting.Results
Mice receiving an elastase-pretreated aorta developed aneurysms and exhibited a significantly increased diastolic vessel diameter compared to control grafted mice at 7 week after surgery (1.11±0.10 mm vs. 0.75±0.03 mm; p≤0,001). Histopathological examination revealed disruption of medial elastin, an increase in collagen content and smooth muscle cells, and neointima formation in aneurysm grafts.Conclusions
We developed a reproducible murine model of elastase-induced aneurysm combined with aortic transplantation. This model may be suitable to investigate aneurysm-specific inflammatory processes and for use in gene-targeted animals. 相似文献18.
Aims
Inflammatory infiltrates and pro-inflammatory mediators are found increased in obstructive and functional bowel disorders, in which lumen distention is present. However, what caused the low level inflammation is not well known. We tested the hypothesis that lumen distention- associated mechanical stress may induce expression of specific inflammatory mediators in gut smooth muscle.Methods
Static mechanical stretch (18% elongation) was applied in vitro in primary culture of rat colonic circular smooth muscle cells (RCCSMCs) with a Flexercell FX-4000 Tension Plus System. Mechanical distention in vivo was induced in rats with an obstruction band placed in the distal colon.Results
In the primary culture of RCCSMCs, we found that static stretch significantly induced mRNA expression of iNOS, IL-6, and MCP-1 in 3 hours by 6.0(±1.4), 2.5(±0.5), and 2.2(±0.5) fold (n = 6∼8, p<0.05), respectively. However, gene expression of TNF-α, IL-1β, and IL-8 was not significantly affected by mechanical stretch. In the in vivo model of colon obstruction, we found that gene expression of iNOS, IL-6, and MCP-1 is also significantly increased in a time-dependent manner in the mechanically distended proximal segment, but not in the sham controls or distal segments. The conditioned medium from the muscle strips of the stretched proximal segment, but not the distal segment or control, significantly induced translocation and phosphorylation of NF-κB p65. This treatment further increased mRNA expression of inflammatory mediators in the naïve cells. However, treatment of the conditioned medium from the proximal segment with neutralizing antibody against rat IL-6 significantly attenuated the activation of NF-κB and gene expression of inflammatory mediators.Conclusions
Our studies demonstrate that mechanical stress induces gene expression of inflammatory mediators i.e. iNOS, IL-6, and MCP-1 in colonic SMC. Further ex vivo study showed that mechanical stress functions as a pro-inflammatory stimulus in the gut. 相似文献19.
[Purpose]
This study was designed to determine the appropriate Leucine intake volume to obtain the effects of restoring damaged muscle through the synthesis of muscle proteins to increase skeletal muscle and improve exercise performance, and to achieve enhanced muscle hypertrophy.[Methods]
To clarify the effects of leucine on skeletal muscle hypertrophy of SD rats, following eight weeks of resistance exercise (climbing ladder), the mass of the FHL (Flexor hallucis longus) was measured after extraction, after which change in the activity of muscle signaling proteins (PKB/Akt, mTOR, p70S6K, 4EBP1) was analyzed.[Results]
The expressions of PKB/Akt, mTOR and p70S6K were increased in L5 (Leucine 50% administration group) compared with the control group (CON) and exercise group (Ex, exercise training group); EL1 (exercise + 10% leucine administration group) and EL5 (exercise + 50% Leucine administration) also exhibited increased expressions of PKB/Akt, mTOR, and p70S6K, while no difference between EL1 and EL5 were observed. No significant differences in 4EBP1 were found among any of the groups. In addition, there were no differences in FHL mass, while relative mass (FHL/body mass) was increased in the exercise group (Ex, EL1, EL5) compared with the control group. No differences were observed among the exercise groups.[Conclusion]
The present study demonstrated that the relative body mass was increased in the EX group compared with the CON group, while no significant differences in muscle mass could be found among the groups. Even though some signaling proteins were increased, or some differences existed among groups, there were no differences in muscle mass between the leucine administration and exercise training combined with leucine administration groups in the present study. 相似文献20.