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.     

Gastroprotective effect of leptin on gastric mucosal injury induced by ischemia-reperfusion is related to gastric histamine content in rats

Leptin has cytoprotective effect to gastric mucosal injury in rats. We aimed to test the hypothesis that leptin induced histamine is involved in the prevention of ischemia-reperfusion (I/R) induced gastric mucosal injury in rats. At the end of the 30 min celiac artery occlusion and 12h reperfusion process, serum and gastric tissue samples were taken from three group of rats to measure oxidative status, histamine levels and for histological examinations. Leptin decreased ulcer and polymorphonuclear leukocyte (PMNL) index, and serum malondialdehyde (MDA) and protein carbonyl content but increased gastric tissue histamine levels. We concluded that leptin exerts a protective effect on gastric mucosa to I/R induced gastric injury probably through increasing tissue histamine content which, in turn, maintain the gastric mucosal blood flow.     

The protective mechanisms of defibrotide on liver ischaemia-reperfusion injury

During some surgical interventions, temporary occlusion of the hepatic blood supply may cause ischaemia-reperfusion (I/R) injury and hepatic dysfunction. In this study the protective effect of defibrotide (DEF) was evaluated in a rat model of liver I/R injury. Four groups of rats were subjected to the following protocols: saline infusion without ischaemia, DEF infusion without ischaemia, DEF infusion with hepatic I/R, and saline infusion with hepatic I/R. After a midline laporatomy, liver ischaemia was induced by 45 min of portal occlusion. DEF 175 mg/kg(-1) was infused before ischaemia in 10 ml of saline. The same volume of saline was infused into the control animals. At the end of the 45-min reperfusion interval, the animals were sacrified. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities were determined in haemolysates, and malondialdehyde (MDA) level in the liver tissue was measured. Tissue MDA levels were significantly higher in the I/R plus saline group compared to the sham operation control groups (p < 0.01 and p < 0.05, respectively). Tissue MDA levels decreased in the DEF plus I/R group compared to the I/R plus saline group (p < 0.05), but DEF could not reduce tissue lipid peroxidation to the levels of the control sham operation groups. SOD and GSH-Px enzyme activities were significantly higher in DEF-treated animals than in the other groups (p < 0.05). These results suggest that DEF protects liver against I/R injury by increasing the antioxidant enzyme levels.     

TNF-alpha and leptin in experimental liver fibrosis models induced by carbon tetrachloride and by common bile duct ligation

In this study we investigated TNF-alpha and leptin levels in two different liver fibrosis models induced by carbon tetrachloride (CCl(4)) and common bile duct ligation (CBDL). A total of 36 male rats of Albino-Wistar strain were allocated to three groups. One of the groups was the control. The second group received 0.15 ml 100 g(-1) CCl(4) subcutaneously for 6 weeks, 3 days per week. The third group underwent common bile duct ligation (CBDL) and was monitored for 4 weeks. Histopathological investigation included fibrosis, steatosis and inflammation. Serum IL-6 and TNF-alpha levels were analysed by ELISA methods and leptin was analysed by RIA. Fibrosis and steatosis increased significantly in the CCl(4) group in comparison with the CBDL group (p < 0.01; p < 0.001). Leptin and TNF-alpha levels in CCl(4) group were higher than those in the CBDL and control groups (p < 0.05). TNF-alpha and leptin levels were not related to each another in either the CCl(4) group or the CBDL group (r=0.22, p > 0.05; r=0.19, p > 0.05). The IL-6 level was higher in the CCl(4) group in relation to severity of inflammation (p < 0.05). TNF-alpha and leptin levels were higher in animals with liver fibrosis induced by CCl(4), than they were in those whose liver fibrosis was induced by common bile duct ligation. Leptin and TNF-alpha may be less effective on the development of liver fibrosis in the group which underwent common bile duct ligation.     

The effect of taurine on renal ischemia/reperfusion injury

Summary. Ischemia-reperfusion (I/R) injury is one of the most common causes of renal dysfunction. Taurine is an endogenous antioxidant and a membrane-stabilizing, intracellular, free beta-amino acid. It has been demonstrated to have protective effects against I/R injuries to tissues other than kidney. The aim of this study was to determine whether taurine has a beneficial role in renal I/R injury. Forty Wistar-Albino rats were allocated into four groups as follows: sham, taurine, I/R, and I/R + taurine. Taurine 7.5 mg/kg was given intra-peritoneally to rats in the groups taurine and I/R + taurine. Renal I/R was achieved by occluding the renal arteries bilaterally for 40 min, followed by 6 h of reperfusion. Immediately thereafter, blood was drawn and tissue samples were harvested to measure 1) serum levels of BUN and creatinine; 2) serum and/or tissue levels of malondialdehyde (MDA), glutathione (GSH), glucose 6-phosphate dehydrogenase (G-6PD), 6-phosphogluconate dehydrogenase (6-PGD) and glutathione reductase (GSH-red); 3) renal morphology; and 4) immunohistochemical staining for P-selectin. Taurine administration reduced I/R-induced increases in serum BUN and creatinine, and serum and tissue MDA levels (p < 0.05). Additionally, taurine lessened the reductions in serum and tissue glutathione levels secondary to I/R (p < 0.05). Taurine also attenuated histopathologic evidence of renal injury, and reduced I/R-induced P-selectin immunoreactivity (p < 0.05). Overall, then, taurine administration appears to reduce the injurious effects of I/R on kidney.     

The protective effect of oxytocin on renal ischemia/reperfusion injury in rats

AIM: Oxytocin was previously shown to have anti-inflammatory effects in different inflammation models. The major objective of the present study was to evaluate the protective role of oxytocin (OT) in protecting the kidney against ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: Male Wistar albino rats (250-300 g) were unilaterally nephrectomized, and subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. OT (1 mg/kg, ip) or vehicle was administered 15 min prior to ischemia and was repeated immediately before the reperfusion period. At the end of the reperfusion period, rats were decapitated and kidney samples were taken for histological examination or determination of malondialdehyde (MDA), an end product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, an index of tissue neutrophil infiltration. Creatinine and urea concentrations in blood were measured for the evaluation of renal function, while TNF-alpha and lactate dehydrogenase (LDH) levels were determined to evaluate generalized tissue damage. Formation of reactive oxygen species in renal tissue samples was monitored by chemiluminescence technique using luminol and lucigenin probes. RESULTS: The results revealed that I/R injury increased (p<0.01-0.001) serum urea, creatinine, TNF-alpha and LDH levels, as well as MDA, MPO and reactive oxygen radical levels in the renal tissue, while decreasing renal GSH content. However, alterations in these biochemical and histopathological indices due to I/R injury were attenuated by OT treatment (p<0.05-0.001). CONCLUSIONS: Since OT administration improved renal function and microscopic damage, along with the alleviation of oxidant tissue responses, it appears that oxytocin protects renal tissue against I/R-induced oxidative damage.     

The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats

The aim of the present study was to evaluate the effects of phosphodiesterase type 5 (PDE5) inhibitory drugs, Tadalafil and Sildenafil, on inducible NOS (iNOS), endothelial NOS (eNOS) and p53 genes expressions and apoptosis in ischemia/reperfusion (I/R) induced oxidative injury in rat renal tissue. Eighty Sprague-Dawley rats (300-350?g) were divided into four groups. In ischemia/reperfusion group, rats were subjected to renal ischemia by clamping the left pedicle for 60?min, and then reperfused for 90?min. On the other hand, in other two groups the rats were individually pretreated with Tadalafil and Sildenafil 1?h before the induction of ischemia. Malondialdehyde (MDA) is determined in renal tissue homogenates by high-performance liquid chromatography, the number of apoptotic cell were calculated by TUNEL method and p53 and eNOS expression were detected with immunohistochemistry. On the other hand, myeloperoxidase (MPO) levels were measured by spectrophotometric method and the mRNA level of iNOS in renal tissue was determined by Real-time PCR (RT-PCR). Our results indicate that MDA and MPO levels were increased in the I/R group than those in the control group. Both Tadalafil and Sildenafil treatment decreased the MDA levels in ischemia/reperfusion group, whereas this effect was more potent with Sildenafil. RT-PCR results showed that, iNOS gen expression increased in the I/R group, but decreased in the PDE5 inhibitory drugs treated group. Apoptotic cells, eNOS levels and p53 positive cells were also decreased in PDE5 inhibitory drugs treated group. We suggest that Tadalafil and Sildenafil have beneficial effects against I/R related renal tissue injury and this protective effect is clearer for Sildenafil than Tadalafil.     

Effects of aminoguanidine against renal ischaemia-reperfusion injury in rats

Aminoguanidine is an inhibitor of nitric oxide synthase (NOS), with high selectivity for the inducible isoform (iNOS). In addition to being an inhibitor of NOS, aminoguanidine also exhibits antioxidant activity. Recent studies suggest that aminoguanidine reduces ischaemia-reperfusion (I/R)-induced damage. However, the role of aminoguanidine, in renal injury associated with I/R remains unknown. This study was designed to investigate the effects of aminoguanidine on renal I/R injury. There were three groups of eight rats each. I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24 h reperfusion in rats. Malondialdehyde (MDA) levels, a stable metabolite of the free radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (30.3 +/- 0.1 nmol g(-1) tissue) than in the control group (10 +/- 0.05 nmol g(-1)). Aminoguanidine (100 mg kg(-1)) administration to rats significantly reduced the MDA values. We also demonstrated that I/R leads to structural change but aminoguanidine did not reverse this change. Aminoguanidine, according to the biochemical finding is protective but histopathological findings did not reveal protection against I/R injury in kidney. The effects of aminoguanidine on I/R-induced damage remain a subject for future investigations.     

Oxytocin alleviates hepatic ischemia-reperfusion injury in rats

Various mechanisms have been proposed for the pathogenesis of postischemic hepatic injury, including the generation of reactive oxygen metabolites. Oxytocin (OT) possesses antisecretory, antiulcer effects, facilitates wound healing and has anti-inflammatory properties. Hepatic ischemia-reperfusion (I/R)-injury was induced by inflow occlusion to median and left liver lobes ( approximately 70%) for 30 min of ischemia followed by 1h reperfusion in female Sprague-Dawley rats under anesthesia. I/R group (n=8) was administered intraperitoneally either OT (500 microg/kg) or saline at 24 and 12 h before I/R and immediately before reperfusion. Sham-operated group that underwent laparotomy without hepatic ischemia served as the control. Rats were decapitated at the end of reperfusion period. Hepatic samples were obtained for the measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH) and collagen levels and histopathological analysis. Tumor necrosis factor-alfa (TNF-alpha) and transaminases (SGOT, SGPT) were assayed in serum samples. I/R injury caused significant increases in hepatic microscopic damage scores, MPO activity, collagen levels, transaminase, serum TNF-alpha levels. Oxytocin treatment significantly reversed the I/R-induced elevations in serum transaminase and TNF-alpha levels and in hepatic MPO and collagen levels, and reduced the hepatic damage scores. OT treatment had tendency to abolish I/R-induced increase in MDA levels, while GSH levels were not altered. These results suggest that OT has a protective role in hepatic I/R injury and its protective effect in the liver appears to be dependent on its inhibitory effect on neutrophil infiltration.     

Mesna (2-mercaptoethane sulfonate) prevents ischemia/reperfusion induced renal oxidative damage in rats

Reoxygenation of the ischemic tissue promotes the generation of various reactive oxygen metabolites (ROM) which are known to have deleterious effects on various cellular functions. This study was designed to determine the possible protective effect of mesna (2-Mercaptoethane Sulfonate) on renal ischemia/reperfusion (I/R) injury. Wistar albino rats were unilaterally nephrectomized, and 15 days later they were subjected to 45 min of renal pedicle occlusion followed by 6 h of reperfusion. Mesna (MESNA, 150 mg/kg, i.p.; an effective dose against I/R injury) or vehicle was administered twice, 15 min prior to ischemia and immediately before the reperfusion period. At the end of the reperfusion period, rats were killed by decapitation. Kidney samples were taken for histological examination or determination of the free radicals, renal malondialdehyde (MDA) and glutathione (GSH) levels, and myeloperoxidase (MPO) activity. Renal tissue collagen content, as a fibrosis marker was also determined. Creatinine and urea concentrations in blood were measured for the evaluation of renal function. The results demonstrated that renal I/R caused nephrotoxicity, as evidenced by increases in blood urea and creatinine levels, which was reversed by MESNA treatment. Increased free radical levels, as assessed by nitroblue-tetrazolium test were reduced with MESNA. Moreover, the decrease in GSH and increases in MDA levels, and MPO activity induced by I/R indicated that renal injury involves free radical formation. Treatment of rats with MESNA restored the reduced GSH levels while it decreased MDA levels as well as MPO activity. Increased collagen contents of the kidney tissues by I/R were reversed back to the control levels by MESNA treatment. Since MESNA administration reversed these oxidant responses, improved renal function and microscopic damage, it seems likely that MESNA protects kidney tissue against I/R induced oxidative damage.     

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.     

Protective effects of taurine against renal ischemia/reperfusion injury in rats by inhibition of gelatinases,MMP-2 and MMP-9, and p38 mitogen-activated protein kinase signaling

Dysregulated expression of matrix metalloproteinases (MMPs) is closely associated with the pathogenesis of renal ischemia/reperfusion injury (I/R). The production of excessive reactive oxygen species (ROS) causes tissue damage. Increased ROS production causes activation of p38 mitogen-activated protein kinase (MAPK) signaling, which participates in gene regulation of MMPs, especially MMP-2 and MMP-9 (gelatinases). Taurine (2-aminoethanesulfonic acid) in mammalian cells functions in bile acid conjugation, maintenance of calcium homeostasis, osmoregulation, membrane stabilization, and antioxidation, antiinflammatory, and antiapoptotic action. We investigated the effects of taurine and the possible role of p38 MAPK signaling on regulation of MMP-2 and MMP-9 in a renal I/R injury model in rats. Rats were divided into three groups: sham, I/R, and I/R + taurine treated. After a right nephrectomy, I/R was induced by clamping the left renal pedicle for 1 h followed by 6 h reperfusion. Taurine was administered 45 min prior to induction of ischemia. Renal function was assessed by serum creatinine and blood urea nitrogen (BUN) levels. Tubule injury and structural changes were evaluated by light microscopy. Malondialdehyde (MDA) levels were analyzed by high performance liquid chromatography (HPLC). Superoxide dismutase (SOD) activity levels were measured using a colorimetric kit. mRNA expression of MMP-2 and MMP-9 was determined by real-time polymerase chain reaction. MMP-2 and MMP-9 activities were measured using a fluorimetric kit. Phosphorylated p38 (p-p38) and total p38 MAPK protein expressions were evaluated by western blot. Taurine pretreatment significantly attenuated renal dysfunction and histologic damage, such as renal tubule dilation and loss of brush borders. The pretreatment also decreased the MDA level and attenuated the reduction of SOD activity in the kidney during I/R. Taurine pretreatment also decreased significantly both MMP-2 and MMP-9 mRNA expression and MMP-9 activity induced by I/R. In addition, the activity of p38 MAPK signaling was down-regulated significantly by taurine administration. Inhibition of MMP-2 and MMP-9 expression and MMP-9 activity caused by taurine may be associated with suppression of p38 MAPK activation during I/R induced renal injury in rats. Therefore, taurine administration may prove to be a strategy for attenuating renal I/R injury.     

骨髓间充质干细胞对移植肾缺血再灌注损伤保护作用的实验研究

目的 观察骨髓间充质干细胞（MSCs）对移植肾缺血再灌注损伤（IRI）模型修复的保护作用,及其作用机制的思路。方法 （1）采用密度梯度离心法结合贴壁分离法分离培养纯化SD大鼠骨髓MSCs,观察其形态,流式细胞仪检测细胞表面标记,检测骨髓MSCs向成骨和成脂细胞分化的潜能;（2）成年雌性SD大鼠28只,随机分组：正常对照组（control group,n=6）,假手术对照组（sham-operated group,n=6）,移植肾IRI组（vehicle-treated I/R group,n=8）,经尾静脉输注间充质干细胞（MSCs）移植肾IRI组（MSCs-treated via tail vein I/R group,n=8）。检测肾功能指标血尿素氮（BUN）和肌酐（Cr）水平变化,评定肾小管的凋亡指数和增殖指数,测定肾组织起氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性及微量丙二醛（MDA）水平,以及对肾脏病理学变化进行观察。结果 （1）分离培养的骨髓MSCs纯度高、生物学特征稳定;（2）移植肾IRI组肾功能指标（BUN36.9±4.8,Scr279.9±22.6）、氧化应激指标明显升高,组织形态学出现肾间质水肿明显,肾小管上皮细胞空泡样变性,近曲小管管壁肿胀,管腔变小。而经尾静脉输注MSCs移植肾IRI组大鼠肾功能指标（BUN22.6±7.8,Scr223.6±26.7）和氧化应激指标得到明显改善（P〈0.05）,组织形态学肾小管上皮细胞细胞核固缩、碎裂和溶解等细胞坏死和变性征象明显减轻,肾小管上皮细胞增殖指数（PI）高于IRI组,肾小管上皮细胞凋亡指数（AI）低于IRI组,两组间差异有统计学意义（P〈0.05）。结论 骨髓MSCs输注能促进肾脏IRI损伤后肾脏细胞增殖,抑制肾脏细胞凋亡,降低血清Creatinine和BUN,在一定程度上促进IRI后肾功能的恢复,通过抑制氧自由基的生成减轻肾组织的损伤程度,改善肾功能。     

Apocynin Alleviates Renal Ischemia/Reperfusion Injury Through Regulating the Level of Zinc and Metallothionen

The purpose of this research was to evaluate the protective effects of apocynin on renal ischemia/reperfusion (I/R) injury (RI/RI) in rats. Rats preconditioned with apocynin were subjected to renal I/R. Zinc levels in serum and renal tissues, blood urea nitrogen (BUN), and serum creatinine (Scr) were detected. We further measured the activity of superoxide dismutase (SOD); the content of malondialdehyde (MDA), IL-4, IL-6, IL-10, and TNF-α; and the expression of metallothionein (MT) in the renal tissues. Results indicated that the levels of MDA, IL-4, IL-6, IL-10, TNF-α, and MT in the kidney tissue and serum BUN and Scr levels in RI/RI group were significantly higher than those in sham-operated group, while the levels of serum Zn and kidney Zn and SOD were reduced in RI/RI group. Apocynin treatment further decreased the levels of MDA, IL-6, TNF-α, and serum BUN and Scr, whereas it significantly increased the levels of Zn, SOD, IL-4, IL-10, and MT in the kidney tissue and serum Zn. These findings suggest that apocynin might play a protective role against RI/RI in rats through regulating zinc level and MT expression involving in oxidative stress.     

The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver.

In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect.     

心肌缺血／再灌注损伤后血清和心肌组织Leptin水平的变能

目的：观察大鼠心肌缺血／再灌注损伤对血清和心肌组织瘦素（Leptin）表达的影响,探讨Leptin在心肌缺血／再灌注损伤中的作用。方法：建立大鼠心肌缺血／再灌注模型,检测血清乳酸脱氢酶（LDH）和Leptin浓度,并用HE染色和免疫组织化学观察心肌组织病理学及Lepfin表达水平。结果：缺血组、再灌注组血清LDH水平显著升高（P〈0．05）,表明该模型制作成功,造成心肌局部一定程度的损伤。缺血组血清Leptin含量（6．34±2．49）ng／ml显著低于对照组（7．50±2．93ng／ml,P〈0．05）;再灌注后Leptin水平缓慢恢复,于再灌注2h时Leptin达到（8．32±1．74）ng／ml,恢复到损伤前水平（8．38±2．56）ng／ml,且随再灌注时间延长有升高趋势。免疫纽化显示与假手术纽心肌Leptin蛋白表达水平相比,其他四组均有显著降低（P〈0．01）,按缺血45min后再灌注1h组、缺血45min后再灌注3h组、单纯缺血45min组、缺血45min后再灌注2h组依次递减。结论：Leptin在心肌缺血／再灌注损伤后早期45min血中有明显减少,心肌组织中也明显表达下降。心肌组织病理损伤与Leptin的改变可能有一定的关系。     

Involvement of metallothionein in the protection of lung ischemic preconditioning

The aim of the present study was to investigate whether metallothionein was involved in the protection of lung ischemic preconditioning (IP) against lung ischemia-reperfusion (I/R) injury. Adult male Sprague-Dawley rats were randomly divided into 3 groups based upon the intervention (n=8): control group (C), lung I/R group (I/R), lung I/R+IP group (IP). At the end of the experiment, the content of metallothionein was tested in lung tissue. Blood specimens collected from the arteria carotis were tested for the contents of malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and myeloperoxidase (MPO). The pneumocyte apoptosis index (AI) was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL). Ultrastructural changes of lung tissue were observed by using transmission electron microscope. The results showed that in I/R group, the content of metallothionein was decreased (P<0.05), the content of MDA and MPO activity were increased (P<0.01), and SOD activity was decreased (P<0.01), compared with those in control group. IP treatment significantly increased the content of metallothionein (P<0.01), attenuated the MDA level (P<0.05) and MPO activity (P<0.01), and improved SOD activity (P<0.01) in blood serum. The number of TUNEL-positive cells in IP group was significantly reduced compared with that in I/R group (P<0.01). There were abnormal ultrastructural changes in I/R group, which were markedly reversed in IP group. In conclusion, IP may protect lung against I/R injury by inducing the expression of metallothionein.     

瘦素对糖尿病大鼠糖脂代谢及炎性因子的影响

目的: 探讨瘦素对糖尿病大鼠糖脂代谢及相关炎症因子的影响。方法: 将健康Wistar雄性大鼠60只随机选取10只作为对照组,50只给予高糖高脂饲料喂养加腹腔内注射链脲佐霉素(STZ,25 mg/kg)的方法诱发并建立糖尿病大鼠模型。并随机分为模型组、瘦素低剂量组、瘦素中剂量组和瘦素高剂量组,每组10只。4组大鼠造模成功后均持续给予高糖高脂饲料喂养,瘦素低、中、高剂量组给予20 μg/kg、50 μg/kg和100 μg/kg,连续5 d。GOD-PAP法检测大鼠血糖(FBG),放射免疫法测定胰岛素含量(Ins),全自动生化分析仪测定血清中三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)、高密度脂蛋白(HDL-C)。采用酶联免疫方法(ELISA)测定丙二醛(MDA)、白细胞介素-6(IL-6)及肿瘤坏死因子-α(TNF-α)。采用Western blot检测糖尿病大鼠脂肪组织中瘦素表达情况。结果: 与对照组比较,各组大鼠血糖水平均显著升高(P＜0.01);与模型组比较,瘦素中、高剂量大鼠血糖显著降低(P＜0.05,P＜0.01);瘦素高剂量组胰岛素水平显著降低(P＜0.01)。不同剂量瘦素组间比较,给药后三组大鼠FBG及INS无统计学差异(P＞0.05)。与模型组比较,瘦素中、高剂量组TC水平显著下降(P＜0.05,P＜0.01);高剂量组TG、LDL-C水平显著降低(P＜0.05),高剂量组HDL-C水平显著升高(P＜0.01)。不同剂量瘦素组进行组间比较,高剂量组在降低TC、TG、LDL-C水平,升高HDL-C水平优于中、低剂量组(P＜0.05)。Western blot结果显示,与模型组(52.27±10.93)比,瘦素高剂量组100 μg/kg(40.13±9.87)、中剂量组50 μg/kg(44.68±10.23)、低剂量组20 μg/kg(47.35±12.09)脂肪中瘦素表达水平依次降低。结论: 瘦素水平分泌异常是诱发糖尿病因素之一,在给予一定浓度外源性瘦素(100 μg/kg)干预下,能显著降低MDA、TNF-α水平,提高IL-6水平,其机制可能与瘦素在减轻炎症反应、氧化应激,纠正血脂异常紊乱有密切关系。     

Growth and anabolic hormones,leptin, and neuromuscular performance in moderately trained prepubescent athletes and untrained boys

We investigated hormonal regulators of growth and development, leptin levels, body composition, neuromuscular performance, and the associations among them in trained prepubertal athletes (experimental group [EG]) and an untrained control group (CG). Informed consent was obtained from the children and their parents. Their maturation stage was evaluated according to Tanner's criteria. There were no differences between EG and CG in physical characteristics, body mass index (BMI), lean body mass, testosterone (T), sex hormone-binding globulin, free androgen index, growth hormone (GH), hand grip strength, and jumping performance. Leptin levels and percent fat of the EG were significantly lower than those of the CG (p < 0.05-0.005). Leptin levels were significantly correlated to body fat and BMI for both the EG and the CG (r = 0.51-0.79). There is little evidence that leptin has a positive effect on growth and anabolic factors. Sex hormone-binding globulin and GH may explain the variation of leptin in athletes with low T (R(2) = 0.43) and in CG (R(2) = 0.35), respectively. Leptin seems to be a permissive factor for the onset of puberty, and the training background needs an optimal biological maturation to produce significant differences in muscle and power performance.     

利格列汀对小鼠脑缺血/再灌注损伤的神经保护作用*

目的: 评估二肽基肽酶4(DPP-4)抑制剂利格列汀对小鼠脑缺血/再灌注(I/R)损伤的神经保护作用。方法: BALB/c小鼠随机分为Sham组、I/R组和利格列汀(2.5、5和10 mg/kg) +I/R组,每组均为8只小鼠。不同剂量利格列汀组小鼠均在I/R前3周连续灌胃给药。采用小鼠脑中动脉闭塞(MCAO)1 h诱导I/R损伤模型,再灌注24 h评估神经功能缺损(n=8)和及梗死体积(n=4);再灌注48 h处死小鼠,检测脑组织中谷胱甘肽(GSH)、丙二醛(MDA)、磷酸化肌醇3激酶(PI3K)、磷酸化蛋白激酶 B(p-Akt)和雷帕霉素靶蛋白(mTOR)含量(n=4)。结果: 与I/R组相比,利他列汀预处理组小鼠再灌注24 h后,神经功能缺损评分和梗死体积明显降低(P＜0.05);小鼠再灌注48 h后,脑内MDA含量明显降低(P＜0.05),而GSH、PI3K、p-Akt和mTOR水平明显升高(P＜0.05)。结论: 利格列汀对I/R小鼠具有神经保护作用,可能是通过激活PI3K/AKT/mTOR通路发挥的作用。