The role of oxygen-free radical in the apoptosis of enterocytes and bacterial translocation in abdominal compartment syndrome

Background: The purpose of this study was to study the impact of intra-abdominal hypertension (IAH) on the intestine.

Materials and methods: One hundred and twenty Sprague-Daley rats were divided into four groups. In the ACS group, the intra-abdominal pressure (IAP) was increased to 20 mmHg. In the ACS/DE group, increased IAP was followed by decompression. In the control1 and control2 groups, the IAP remained unchanged. Malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH) and glutathione peroxidase (GSH-Px) enzymes of the intestine were measured. Additionally, ileal tissues were obtained for histopathological examinations and apoptosis detection. Liver, spleen and mesenteric lymph nodes were obtained for microbiological analysis.

Results: In the presence of IAH, MDA and MPO were increased, while GSH and GSH-Px were decreased. Microbiological analysis suggested bacterial translocation across the gut. Morphological examinations indicated that the Chiu's score and apoptotic index in the ACS/DE group were the highest in the four groups.

Conclusions: Oxidative stress plays an important role in the intestinal damage and bacterial translocation in abdominal compartment syndrome. Additionally, the influence of oxygen free radicals occurs mainly during the period of reperfusion rather than during the IAH period.     

Abdominal compartment syndrome in polytrauma

Authors inform about the group of 8 patients with abdominal compartment syndrome (ACS) occurred as a complication in large blunt injury of abdominal cavity. To the ACS diagnose, the measurement of intracystic pressure is used routinely, whose values correlate fully with values of intraabdominal pressure (IAP). In case of increasing values of IAP over 25 mm Hg with positive clinical signs of ACS, authors indicate decompression laparotomy with temporary closing of abdominal cavity by sterile plastic foil or Ethizip. This preventive temporary laparostomy is recommended also in serious injuries of abdominal cavity in patients with fatal haemorrhage, treated by the method of staged laparotomy with tamponade of abdominal cavity and with massive blood and volume resuscitation.     

The Effects of Intra-Abdominal Hypertension on the Secretory Function of Canine Adrenal Glands

Intra-abdominal hypertension (IAH) can damage multiple organ systems, but the explicit impact on the adrenal gland is unclear. To evaluate the effects of intra-abdominal pressure (IAP) on the secretory function of the adrenal glands, we established canine models of IAH. By comparing morphology; hemodynamics; plasma cortisol, aldosterone, epinephrine, and norepinephrine concentrations; and the expression of IL-1, IL-6, and TNF-α in adrenal gland tissue from these dogs, we found that hemodynamic instability occurred after IAH and that IAH increased the plasma cortisol, aldosterone, epinephrine, and norepinephrine concentrations. Higher IAPs resulted in more significant changes, and the above indicators gradually returned to normal 2 h after decompression. Compared with the sham-operated group, IAH significantly increased IL-1, IL-6, and TNF-α levels in adrenal tissue, with larger increases in the presence of higher IAPs. However, the concentrations of these markers remained higher than those in the sham-operated group despite their decrease after 2 h of decompression. Histopathological examination revealed congestion, red blood cell exudation, and neutrophil infiltration in the adrenal glands when IAP was elevated; these conditions became more significant with more severe IAH. These results suggest that the secretion of adrenal hormones and adrenal gland inflammation are positively correlated with IAP and that abdominal decompression effectively corrects adrenal gland function.     

Quercetin treatment against ischemia/reperfusion injury in rat corpus cavernosum tissue: a role on apoptosis and oxidative stress

Abstract

Reactive oxygen metabolites play an important role in the ischemia/reperfusion (I/R)-induced tissue injury. This study was designed to investigate the possible protective effects of quercetin against I/R injury of the rat corpus cavernosum tissue. To induce I/R injury, abdominal aorta was clamped for 30 min and reperfused for 60 min. Quercetin (20 mg/kg) or vehicle was given before ischemia and just after reperfusion in the I/R group and in the sham-operated control group in which clamping was not performed. After decapitation, corpus cavernosum tissues were removed and either placed in organ baths or stored for evaluating biochemical parameters. Oxidative injury was examined by measuring lucigenin chemiluminescence (CL), nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities and caspase-3 protein levels. In the I/R group, contractile responses to phenylephrine and relaxation responses to carbachol were impaired significantly compared with those in the control groups, while quercetin treatment in I/R group reversed both of the responses. On the other hand, increase in lucigenin CL, NO, MDA levels and MPO and caspase-3 activities and decrease in GSH levels and SOD activity in the cavernosal tissues of the I/R group were also significantly reversed by quercetin treatment. Furthermore, observed distorted morphology with ruptured endothelial cells and vacuolization in the cytoplasm of cavernosal tissues of I/R no longer persisted in the quercetin-treated I/R group. Thus, our results suggested that treatment with quercetin may have some benefits in controlling I/R-induced tissue injury through its anti-inflammatory, anti-apoptotic, and antioxidant effects.     

The effect of intra-abdominal hypertension incorporating severe acute pancreatitis in a porcine model

Introduction

Abdominal compartment syndrome (ACS) and intra abdominal hypertension(IAH) are common clinical findings in patients with severe acute pancreatitis(SAP). It is thought that an increased intra abdominal pressure(IAP) is associated with poor prognosis in SAP patients. But the detailed effect of IAH/ACS on different organ system is not clear. The aim of this study was to assess the effect of SAP combined with IAH on hemodynamics, systemic oxygenation, and organ damage in a 12 h lasting porcine model.

Measurements and Methods

Following baseline registrations, a total of 30 animals were divided into 5 groups (6 animals in each group): SAP+IAP30 group, SAP+IAP20 group, SAP group, IAP30 group(sham-operated but without SAP) and sham-operated group. We used a N₂ pneumoperitoneum to induce different levels of IAH and retrograde intra-ductal infusion of sodium taurocholate to induce SAP. The investigation period was 12 h. Hemodynamic parameters (CO, HR, MAP, CVP), urine output, oxygenation parameters(e.g., S_vO₂, PO₂, PaCO₂), peak inspiratory pressure, as well as serum parameters (e.g., ALT, amylase, lactate, creatinine) were recorded. Histological examination of liver, intestine, pancreas, and lung was performed.

Main Results

Cardiac output significantly decreased in the SAP+IAH animals compared with other groups. Furthermore, AST, creatinine, SUN and lactate showed similar increasing tendency paralleled with profoundly decrease in S_vO₂. The histopathological analyses also revealed higher grade injury of liver, intestine, pancreas and lung in the SAP+IAH groups. However, few differences were found between the two SAP+IAH groups with different levels of IAP.

Conclusions

Our newly developed porcine SAP+IAH model demonstrated that there were remarkable effects on global hemodynamics, oxygenation and organ function in response to sustained IAH of 12 h combined with SAP. Moreover, our model should be helpful to study the mechanisms of IAH/ACS-induced exacerbation and to optimize the treatment strategies for counteracting the development of organ dysfunction.     

Inverted U-Shaped Relationship between Central Venous Pressure and Intra-Abdominal Pressure in the Early Phase of Severe Acute Pancreatitis: A Retrospective Study

Objective

Many studies have indicated that intra-abdominal pressure (IAP) is positively correlated with central venous pressure (CVP) in severe cases. However, although elevated IAP is common in patients with severe acute pancreatitis (SAP), its relationship with CVP remains unclear. Our study aimed to investigate the association of IAP with CVP in early-phase SAP patients.

Methods

In total, 116 SAP patients were included in this retrospective study. On the first day of hospitalization, blood samples were collected for biochemical examination and cytokine concentration monitoring. Additionally, a urinary catheter and right subclavian vein catheter were inserted for IAP and CVP measurement, respectively. Other routine clinical data were also recorded.

Results

Within 24 hours after hospitalization, CVP fluctuated and increased with increasing IAP up to 15.7 mmHg (P = 0.054) but decreased with increasing IAP when the IAP was > 15.7 mmHg (P < 0.001). After adjusting for abdominal perfusion pressure (APP) and mean arterial pressure (MAP), a similar distribution was observed. An inverted U-shaped trend between IAP and CVP was also present in the groups classified according to the patient’s sex, local complications, ascites, and serum amylase levels.

Conclusions

CVP and IAP have an inverted U-shaped relationship, with a peak at an IAP of 15.7 mmHg in the early phase of SAP. After this peak, CVP decreases as IAP increases. These results have crucial implications for clinical fluid resuscitation in SAP patients. In particular, because one CVP value might be correlated with different IAP values in patients with the same CVP, the volume of fluid needed might be different.     

Role of leukocyte accumulation and oxygen radicals in ischemia-reperfusion-induced injury in skeletal muscle

The role of leukocytes and nonleukocyte-derived reactive oxygen metabolites (ROMs) in reperfusion-induced skeletal muscle injury was determined. Male rats received 2 h no-flow hindlimb ischemia-reperfusion (I/R, n = 6) or were rendered neutropenic via antineutrophil serum (ANS) before I/R (I/R + ANS, n = 5). Oxygen radicals in the absence of neutrophils were tested by administration of dimethylthiourea (DMTU) (I/R + ANS + DMTU, n = 5). Perfused capillaries (CD(per)) and rolling (L(r)), adherent (L(a)), and extravasated leukocytes (L(e)) in the extensor digitorum longus muscle were measured every 15 min during 90 min of reperfusion using intravital microscopy. The vital dyes bisbenzimide (BB) and ethidium bromide (EB) provided direct measures of tissue injury (EB/BB). CD(per) decreased immediately on reperfusion in the I/R and I/R + ANS groups. CD(per) in the I/R + ANS + DMTU group remained at baseline throughout reperfusion. L(a) increased in the I/R group; however, EB/BB was the same between I/R and I/R + ANS groups. Injury in the I/R + ANS + DMTU group did not differ from other groups > or =60 min, after which EB/BB became significantly lower. L(e) did not differ between groups and was highly correlated to tissue injury. The results suggest that L(e) lead to parenchymal injury, and ROMs lead to perfusion deficits during the early reperfusion period after ischemia.     

Protective effects of intermedin/adrenomedullin2 on ischemia/reperfusion injury in isolated rat hearts

Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family identified from human and other vertebrate tissues. Preprointermedin can generate a 47-amino acid mature peptide (IMD(1-47)) and a shorter 40-amino acid one (IMD(8-47)) by proteolytic cleavage. The present study was designed to determine the protective effect of IMD on cardiac ischemia/reperfusion (I/R) injury and its possible mechanism. Isolated rat hearts were perfused on a Langendorff apparatus and subjected to 45-min global ischemia and 30-min reperfusion. Cardiac function was measured. The release of myocardial protein and lactate dehydrogenase (LDH) and the formation of malondialdehyde (MDA) were assayed. Myocardial cAMP content was determined by radioimmunoassay (RIA). Cardiac I/R induced a marked inhibition of cardiac function and myocardial injury. Reperfusion with IMD significantly attenuated the I/R injury. Compared with I/R alone, perfusion with 10(-8)mol/L IMD(1-47) and IMD(8-47) induced a 36% and 33% increase in Delta left ventricular pressure (DeltaLVP), 30% and 28% in maximal rate of increase of LV pressure (+LVdP/dt max), and 34% and 31% in maximal rate of decrease of LV pressure (-LVdP/dt max), respectively (all P<0.01) but an approximately 58% and 51% decrease in LV diastolic pressure, respectively (P<0.01). In addition, perfusion with IMD markedly attenuated the leakage of LDH, total protein and myoglobin from myocardia compared with I/R alone. The contents of ventricular myocardia cAMP after reperfusion with 10(-8)mol/L IMD(1-47) and IMD(8-47) were 130% and 91% higher, respectively, than that with I/R alone (all P<0.01). However, formations of myocardial MDA were 52% and 50% lower than that with I/R alone (all P<0.01), respectively. Interestingly, the above IMD effects were similar to those of adrenomedullin (10(-8)mol/L). These results suggest that IMD, like adrenomedullin, exerts cardio-protective effects against myocardial I/R injury.     

Resistance to Systemic Inflammation and Multi Organ Damage after Global Ischemia/Reperfusion in the Arctic Ground Squirrel

Introduction

Cardiac arrest (CA) and hemorrhagic shock (HS) are two clinically relevant situations where the body undergoes global ischemia as blood pressure drops below the threshold necessary for adequate organ perfusion. Resistance to ischemia/reperfusion (I/R) injury is a characteristic of hibernating mammals. The present study sought to determine if arctic ground squirrels (AGS) are protected from systemic inflammation and multi organ damage after CA- or HS-induced global I/R and if, for HS, this protection is dependent upon their hibernation season.

Methods

For CA, rats and summer euthermic AGS (AGS-EU) were asphyxiated for 8 min, inducing CA. For HS, rats, AGS-EU, and winter interbout arousal AGS (AGS-IBA) were subject to HS by withdrawing blood to a mean arterial pressure of 35 mmHg and maintaining that pressure for 20 min before reperfusion with Ringers. For both I/R models, body temperature (Tb) was kept at 36.5–37.5°C. After reperfusion, animals were monitored for seven days (CA) or 3 hrs (HS) then tissues and blood were collected for histopathology, clinical chemistries, and cytokine level analysis (HS only). For the HS studies, additional groups of rats and AGS were monitored for three days after HS to access survival and physiological impairment.

Results

Rats had increased serum markers of liver damage one hour after CA while AGS did not. For HS, AGS survived 72 hours after I/R whereas rats did not survive overnight. Additionally, only rats displayed an inflammatory response after HS. AGS maintained a positive base excess, whereas the base excess in rats was negative during and after hemorrhage.

Conclusions

Regardless of season, AGS are resistant to organ damage, systemic inflammation, and multi organ damage after systemic I/R and this resistance is not dependent on their ability to become decrease Tb during insult but may stem from an altered acid/base and metabolic response during I/R.     

Protective effects of leptin on ischemia/reperfusion injury in rat bladder

The aim of the study was to evaluate protective effects of exogenous leptin on ischemia/reperfusion (I/R)-induced injuries to the urinary bladder tissue and to investigate the effect on tumor necrosis factor alpha (TNF-alpha) levels and apoptotic cells during I/R injury. Bladder I/R injury was induced by abdominal aorta occlusion by ischemia for 45 min, followed by 60 min of reperfusion in rats. The rats were divided into three groups: control (n = 8 + 8), I/R (n = 8 + 8) and I/R+leptin group (n = 8 + 8). The rats in the I/R+leptin group were treated intraperitoneally with leptin (10 microg/kg) 60 min prior to ischemia induction. At the end of the reperfusion period, urinary bladders of the first eight rats from each group were removed for TUNEL staining processing while the others were removed for biochemical analyses for MDA and TNF-alpha levels. In the I/R group, the ratios of TUNEL-positive nuclei were higher than the control and the I/R+leptin groups. The MDA and TNF-alpha levels of the bladder tissue in the I/R group were higher than the control and leptin-treated groups. TUNEL-staining and biochemical studies revealed that leptin has a protective effect on urinary bladder I/R injury.     

老年男性腹股沟疝与肌肉质量、肌力及腹内压的相关性

摘要 目的：探讨老年男性腹股沟疝与肌肉质量、肌力及腹内压力（IAP）的相关性。方法：选取2021年1月-2023年1月在眉山市人民医院普外一科就诊的 86例老年男性腹股沟疝患者作为研究组,选取同期100名老年体检者作为对照组,对两组研究对象的腹部肌肉质量、肌力及IAP进行检测,并探讨其与腹股沟疝发病风险的相关性。结果：研究组患者腹部骨骼肌肉面积值（SMA）、骨骼肌指数（SMI）水平及右手握力、左手握力均低于对照组,腹内脂肪面积、SMI异常比例及直立加压时腹内压（OVIAP）、直立加压前后腹内压差（OVIAPD）、平卧与直立加压时腹内压差（OSVIAPD）均高于对照组,差异均有统计学意义（P<0.05）。Logistic多元回归模型分析结果显示,老年腹股沟疝的发生与SMI水平、SMI异常、右手握力、OVIAPD、OSVIAPD具有相关性（P<0.05）。结论：老年男性腹股沟疝患者存在腹部肌肉质量和肌力的下降,患者在直立做加压动作时可出现IAP水平的升高,上述指标均与腹股沟疝的发生具有相关性,临床可采用针对性的综合干预措施以降低老年男性人群腹股沟疝的发病风险。     

黑木耳多糖对抗离体心脏缺血/再灌注损伤的研究

目的:探讨黑木耳多糖(AAP)对离体大鼠心脏缺血/再灌注(I/R)损伤的防护作用及其机制。方法:健康雄性SD大鼠灌胃黑木耳多糖(50,100,200mg/(kg.d))4周后,采用离体心脏Langendorff灌流方法,全心停灌30min,复灌120min建立I/R模型。测定左心室动力学指标和再灌注各时间点冠脉流出液中乳酸脱氢酶(LDH)含量;实验结束测定心肌组织甲月赞(formazan)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性的变化。结果:与单纯I/R组相比,AAP预处理明显提高心肌细胞的formazan含量,降低再灌注期间冠脉流出液中LDH含量,明显增强左室发展压、左心室内压最大上升速率和心率与发展压乘积的恢复,缓解冠脉流量的减少;高剂量AAP改善I/R心肌功能的作用要好于丹参预处理(4ml/(kg.d),gastricperfusion)组。中剂量AAP(100mg/(kg.d))预处理4周后明显抑制I/R心肌MDA的增加和SOD活性的减弱(P0.01),其效果要好于丹参阳性对照组。结论:在大鼠离体心脏灌流模型上,黑木耳多糖预处理具有抗心脏I/R损伤的作用,这种保护作用可能与其增加心肌SOD活性,减少脂质过氧化损伤有关。     

Effect of Acute,Slightly Increased Intra-Abdominal Pressure on Intestinal Permeability and Oxidative Stress in a Rat Model

IntroductionIntra-abdominal hypertension (IAH) is known as a common, serious complication in critically ill patients. Bacterial translocation and permeability changes are considered the pathophysiological bases for IAH-induced enterogenic endotoxemia and subsequent multiorgan failure. Nevertheless, the effects of slightly elevated intra-abdominal pressures (IAPs) on the intestinal mucosa and the associated mechanisms remain unclear.MethodsTo investigate the acute effects of different nitrogen pneumoperitoneum grades on colonic mucosa, male Sprague-Dawley rats were assigned to six groups with different IAPs (0 [control], 4, 8, 12, 16, and 20 mmHg, n = 6/group). During 90 min of exposure, we dynamically monitored the heart rate and noninvasive hemodynamic parameters. After gradual decompression, arterial blood gas analyses were conducted. Thereafter, structural injuries to the colonic mucosa were identified using light microscopy. Colon permeability was determined using the expression of tight junction proteins, combined with fluorescein isothiocyanate dextran (FD-4) absorption. The pro-oxidant-antioxidant balance was determined based on the levels of malondialdehyde (MDA) and antioxidant enzymes.ResultsIAH significantly affected the histological scores of the colonic mucosa, tight junction protein expression, mucosal permeability, and pro-oxidant-antioxidant balance. Interestingly, elevations of IAP that were lower than the threshold for IAH also showed a similar, undesirable effect. In the 8 mmHg group, mild hyponatremia, hypocalcemia, and hypoxemia occurred, accompanied by reduced blood and abdominal perfusion pressures. Mild microscopic inflammatory infiltration and increased MDA levels were also detected. Moreover, an 8-mm Hg IAP markedly inhibited the expression of tight junction proteins, although no significant differences in FD-4 permeability were observed between the 0- and 8-mmHg groups.ConclusionsAcute exposure to slightly elevated IAP may result in adverse effects on intestinal permeability and the pro-oxidant-antioxidant balance. Therefore, in patients with critical illnesses, IAP should be dynamically monitored and corrected, as soon as possible, to prevent intestinal mucosal injury and subsequent gut-derived sepsis.     

Effects of intermedin(1-53) on cardiac function and ischemia/reperfusion injury in isolated rat hearts

Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family identified from human and other vertebrate tissues. Preprointermedin (preproIMD) can generate a 47 amino acid mature peptide (IMD(1-47)) and a shorter 40 amino acid one (IMD(8-47)) by proteolytic cleavage. Amino acid sequence analysis showed that cleavage sites are located between two basic amino acids at Arg93-Arg94, resulting in the production of preproIMD(95-147), namely IMD(1-53). The present study was designed to observe the effects of IMD(1-53) on cardiac function in ischemia/reperfusion (I/R) injury in isolated rat hearts. Perfusion with high-dose IMD(1-53) gave higher left ventricular systolic pressure (LVSP) and maximal rate of increase and decrease of left ventricle pressure (+/-LVdP/dt(max)), and coronary perfusion flow (CPF) than those of controls. Cardiac I/R induced a marked inhibition of cardiac function and myocardial injury. Reperfusion with IMD(1-53) significantly ameliorated the inhibited cardiac function and bradycardia induced by I/R. Compared with the I/R-treatment alone, IMD(1-53) reperfusion augmented CPF, LVSP, and maximal rate of increase and decrease of left ventricle pressure (+/-LVdP/dt(max)) and decreased LVDP. In addition, reperfusion with IMD(1-53)markedly attenuated the leakage of lactate dehydrogenase and malondialdehyde content in myocardia compared with I/R alone. Reperfusion with IMD(1-53)increased the content of cyclic adenosine monophosphate in comparison with I/R alone. Interestingly, the above IMD(1-53) effects are similar to those of adrenomedullin. These results suggest that IMD(1-53), like adrenomedullin, has cardioprotective effects against myocardial I/R injury.     

Human recombinant erythropoietin protects the striated muscle microcirculation of the dorsal skinfold from postischemic injury in mice

Erythropoietin (EPO) has been proposed as a novel cytoprotectant in ischemia-reperfusion (I/R) injury of the brain, heart, and kidney. However, whether EPO exerts its protection by prevention of postischemic microcirculatory deterioration is unknown. We have investigated the effect of EPO on I/R-induced microcirculatory dysfunctions. We used the mouse dorsal skinfold chamber preparation to study nutritive microcirculation and leukocyte-endothelial cell interaction in striated muscle of the dorsal skinfold by in vivo fluorescence microscopy before 3 h of ischemia and during 5 days of reperfusion. Animals were pretreated with EPO (5,000 U/kg body wt) 1 or 24 h before ischemia. Vehicle-treated I/R-injured animals served as controls. Additional animals underwent sham operation only or were pretreated with EPO but not subjected to I/R. I/R significantly (P < 0.05) reduced functional capillary density, increased microvascular permeability, and enhanced venular leukocyte-endothelial cell interaction during early reperfusion. These findings were associated with pronounced (P < 0.05) arteriolar constriction and diminution of blood flow during late reperfusion. Pretreatment with EPO induced EPO receptor and endothelial nitric oxide synthase expression at 6 h of reperfusion (P < 0.05). In parallel, EPO significantly (P < 0.05) reduced capillary perfusion failure and microvascular hyperpermeability during early reperfusion and arteriolar constriction and flow during late reperfusion. EPO pretreatment substantially (P < 0.05) diminished I/R-induced leukocytic inflammation by reducing the number of rolling and firmly adhering leukocytes in postcapillary venules. EPO applied 1 h before ischemia induced angiogenic budding and sprouting at 1 and 3 days of reperfusion and formation of new capillary networks at 5 days of reperfusion. Thus our study demonstrates for the first time that EPO effectively attenuates I/R injury by preserving nutritive perfusion, reducing leukocytic inflammation, and inducing new vessel formation.     

缺血／再灌注损伤对心肌细胞核膜NTPase活性和mRNA出核转运的影响

目的：观察家兔心肌缺血／再灌注（I／R）损伤对心肌细胞核膜核苷三磷酸酶（NTPase）动力学及mRNA出核转运的变化。方法：制备家兔离体心脏I／R模型,密度梯度离心法制备心肌细胞核膜,按Tiffany等的方法测定NTPase活性及mRNA的转运率。结果：心肌细胞核膜NTPase在以ATP或GTP为底物时,与对照组比较,I／R组最大反应速率（Vmax)分别降低26％及22％（P＜0．01）。Km值分别升高54％及72％（P＜0．01）;而缺血组Vmax及Km值较对照组无明显差异。以ATP或GTP启动反应时I／R组10min内心肌细胞核mRNA转出率分别较对照组降低27％及32％（P＜0．01）;而缺血组与对照组相比并无显著性差异（P＞0．05）。结论：心肌缺血／再灌注损伤时,心肌细胞核膜受损,核膜上NTPase活性降低,导致细胞核膜mRNA出核受阻,从而可能影响蛋白质的合成表达。     

β(2)-adrenoreceptor mediates the cardioprotection of ischemic preconditioning on myocardial contraction in rats subjected to ischemia/reperfusion injury

The aim of the present study is to investigate the role of beta(2)-adrenoreceptor (beta(2)-AR) in ischemic preconditioning (IP) in isolated rat heart model of ischemia/reperfusion (I/R). Sprague-Dawley rat hearts were quickly removed, mounted on Langendorff apparatus, and perfused with Krebs-Henseleit (KH) solution. After the initial stabilization period, the rats were randomly divided into 6 groups including control group (perfused for an additional 20 min), IP group (4 cycles of 5 min of ischemia followed by 5 min of reflow), isoproterenol (ISO) group (10 nmol/L ISO perfusion for 5 min followed by 5 min washout), IP + ICI118551 group (55 nmol/L ICI118551 perfusion for 5 min before and throughout IP), ISO + ICI118551 group (55 nmol/L ICI118551 perfusion for 5 min before and throughout ISO treatment), ICI118551 group (55 nmol/L ICI118551 perfusion for 20 min). After these treatments, all hearts were followed by 30 min of no-flow ischemia and 30 min of reperfusion. A computer-based electrophysiological recorder system was used to measure changes of the maximal rate of pressure increase in systole phase (+dp/dt(max)), maximal rate of pressure decrease in diastole phase (-dp/dt(max)), and difference of left ventricular pressure (DeltaLVP). Then cardiomyocytes from these hearts were isolated by 5 min of Ca(2+)-free buffer perfusion and 25 min of collagenase perfusion. The ventricles were chopped and filtered. The myocytes were resuspended in KB buffer. The contraction and the viability of cardiomyocytes were measured. Lactate dehydrogenase (LDH) concentration in coronary effluent was assayed with assay kit. The results showed that both IP and ISO significantly increased the values of +/-dp/dt(max), DeltaLVP, the contraction and viability of cardiomyocytes, shortened the time-to-peak contraction (TTP), and decreased the release of LDH in coronary effluent. ICI118551, a selective beta(2)-AR antagonist, blocked these effects. Either the time-to-50% relaxation (R(50)) or the time-to-100% relaxation (R(100)) had no significant differences between groups. Our results indicate that the cardioprotection of IP was mediated by beta(2)-AR in isolated rat hearts subjected to I/R injury.     

Protective effect of heme oxygenase-1 induction against hepatic injury in alcoholic steatotic liver exposed to cold ischemia/reperfusion

AimsThe purpose of this study was to investigate the cytoprotective role of heme oxygenase-1 (HO-1) induction in hepatic injury in alcoholic steatotic liver exposed to cold ischemia/reperfusion (I/R).Main methodsAnimals were fed an ethanol liquid diet or isocaloric control diet for 5 weeks. Isolated perfused rat livers were preserved in Histidine–Tryptophan–Ketoglutarate at 4 °C. After 24 h of storage, livers were subjected to 120 min of reperfusion with Krebs–Henseleit bicarbonate buffer at 37 °C. Animals were pretreated with cobalt protoporphyrin (CoPP, 5 mg/kg, i.p.) or zinc protoporphyrin (ZnPP, 25 mg/kg, i.p.), HO-1 inducer and antagonist, respectively.Key findingsIn the model of ischemia/isolated perfusion, endogenous HO-1 was downregulated in the livers fed with ethanol diet (ED I/R). In ED I/R group, portal pressure and lactate dehydrogenase release were significantly increased, while bile output and hyaluronic acid clearance decreased compared to rats fed on control diet (CD I/R). Furthermore, hepatic glutathione content decreased and lipid peroxidation increased in the ED I/R group compared to the CD I/R group. These alterations were attenuated by upregulation of HO-1 with CoPP pretreatment.SignificanceOur results suggest that chronic ethanol consumption aggravates hepatic injury during cold I/R and it is likely due to downregulation of endogenous HO-1. Prior induction of HO-1 expression may provide a new strategy to protect livers against hepatic I/R injury or to increase the donor transplant pool through modulation of marginal alcoholic steatotic livers.     

Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels

The present study was undertaken to investigate the protective effect of H2S against myocardial ischemia-reperfusion (I/R) injury and its possible mechanism by using isolated heart perfusion and patch clamp recordings. Rat isolated hearts were Langendorff-perfused and subjected to a 30-minute ischemia insult followed by a 30-minute reperfusion. The heart function was assessed by measuring the LVDP, +/-dP/dt max, and the arrhythmia score. The results showed that the treatment of hearts with a H2S donor (40 micromol/L NaHS) during reperfusion resulted in significant improvement in heart function compared with the I/R group (LVDP recovered to 85.0% +/- 6.4% vs. 35.0% +/- 6.1%, +dP/dt max recovered to 80.9% +/- 4.2% vs. 43.0% +/- 6.4%, and -dP/dt max recovered to 87.4% +/- 7.3% vs. 53.8% +/- 4.9%; p < 0.01). The arrhythmia scores also improved in the NaHS group compared with the I/R group (1.5 +/- 0.2 vs. 4.0 +/- 0.4, respectively; p < 0.001). The cardioprotective effect of NaHS during reperfusion could be blocked by an ATP-sensitive potassium channel (K ATP) blocker (10 micromol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of K ATP channels from 0.07 +/- 0.03 to 0.15 +/- 0.08 after application of 40 mumol/L NaHS and from 0.07 +/- 0.03 to 0.36 +/- 0.15 after application of 100 mumol/L NaHS. These findings provide the first evidence that H2S increases the open probability of K ATP in cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion.     

The effect of ghrelin pretreatment on epididymal sperm quality and tissue antioxidant enzyme activities after testicular ischemia/reperfusion in rats

Ghrelin, the endogenous ligand for growth hormone secretagogue receptor, has been reported to prevent ischemia/reperfusion (I/R) injury in various tissues by its antioxidant activity. Therefore, this study was aimed to investigate the effect of ghrelin on sperm quality and antioxidant enzyme activity in a rat testicular ischemia/reperfusion injury model. Forty-two male Wistar rats were divided into groups control, I/R, and I/R plus ghrelin. The right testes were rotated 720° for 1 h and were allowed to reperfuse for 4 h and 30 days thereafter. Ghrelin (40 nmol/kg IP) or vehicle (physiological saline) was administrated 15 min before reperfusion. After 4 h of reperfusion, a right orchiectomy was performed to measure the biochemical parameters. In addition, the sperm was collected from the epididymis after 30 days of reperfusion, and sperm characteristics were examined. The malondialdehyde levels of the testis tissues were significantly increased, but a statistically significant decrease was found in the superoxide dismutase, glutathione peroxidase, and catalase activities in the I/R group as compared with the control, indicating I/R injury. The sperm evaluation showed a significant reduction in all characteristics resulted from I/R compared with the control. In the ghrelin-treated group, the malondialdehyde values were significantly lowered, and only enzyme activity of glutathione peroxidase showed significant increases compared with the I/R group. Ghrelin significantly enhanced sperm motility, movement, and concentration but did not prevent I/R-induced reduction in membrane integrity in the testes of rats compared to the I/R group. Our results suggest that ghrelin treatment has a protective role on IR-induced testicular injury, and this effect may be due to its antioxidant properties.