细胞色素C在缺血／再灌注损伤中的作用

细胞色素C为线粒体呼吸链复合体Ⅲ的成分，在复合体Ⅲ和Ⅳ之间传递电子。许多因素可刺激细胞色素C从线粒体释放，一旦其释放到胞浆中就可依赖于细胞内ATP水平诱导细胞凋亡或坏死。研究表明缺血／再灌注损伤与细胞色素c释放密切相关。现从细胞色素C的结构和特性、释放及其调控、缺血再灌注损伤对细胞色素C释放的影响以及其在缺血再灌注损伤中的作用等方面进行综述。     

线粒体通透件转换孔在缺血/再灌注损伤中的作用

背景 线粒体作为“能量工厂”提供细胞生长及代谢所需的三磷酸腺苷（adenosine triphosphate,ATP）,同时也是细胞存活与否的重要信号管理者.线粒体通透性转换孔（mitochondrial permeability transition pore,mPTP）是横跨线粒体内外膜之间的允许相对分子质量1.5 kD以下的分子自由通过的孔道.在脑缺血/再灌注（ischemia/reperfusion,I/R）损伤中,线粒体是研究的焦点,而mPTP作为线粒体的门户更是影响着线粒体膜电位（mitochondrial membrane potential,△ψm）、线粒体Ca2＋超载及促细胞死亡物质释放等一系列过程. 目的 对mPTP在I/R损伤中可能的作用机制及治疗方法进行综述. 内容 整理和阐述了mPTP的结构、mPTP与I/R损伤的机制和预防与治疗I/R损伤的可能方法. 趋向 随着mPTP在I/R损伤中的作用机制不断被揭示,其将成为治疗I/R损伤的重要靶点.     

细胞凋亡与肝脏缺血/再灌注损伤

细胞凋亡是肝缺血再灌注过程中的病理特征之一,本文论述在肝缺血/再灌注损伤中肝细胞凋亡的发生机制。     

七氟烷预处理对大鼠离体心肌缺血/再灌注损伤线粒体细胞色素C释放的影响

目的 探讨七氟烷预处理对大鼠离体心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)时心肌细胞凋亡及线粒体细胞色素C释放的影响.方法 40只SD大鼠应用随机数字表法随机分为4组(每组10只):对照组(C组),0.75％、1.5％、3.0％七氟烷预处理组(S1、S2、S3组).应用Langendorff离体心脏灌注模型,经主动脉用Krebs-Henseleit( K-H)液逆行灌注.各组均缺血30 min,再灌注60 min.S1、S2、S3组在缺血前分别以含相应浓度七氟烷的K-H液灌注10 min,再冲洗5 min,重复2次.记录平衡灌注末、缺血前即刻、再灌注30、60 min时的心功能指标.再灌注60 min时用DNA原位末端缺口标记技术(terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling,TUNEL)测定凋亡细胞,提取心肌线粒体,免疫印迹法测定线粒体和胞浆的细胞色素C水平.结果 与C组比较,S1、S2、S3组再灌注30、60 min时左室舒张末压(left ventricular end-diastolic pressure,LVEDP)降低、左室发展压(left ventricular developed pressure,LVDP)升高(P＜0.05);与C组比较,S1、S2、S3组凋亡率明显下降(P＜0.05或0.01),再灌注末心肌细胞凋亡率C、S1、S2、S3组分别为(33.10±2.57)％、(28.03±3.11)％、(25.20±3.04)％、(24.06±2.58)％;与C组比较,S1、S2、S3组心肌线粒体细胞色素C释放减少,胞浆细胞色素C的量明显降低(P＜0.05或0.01).结论 七氟烷预处理能够通过抑制心肌线粒体细胞色素C释放到胞浆,降低心肌细胞凋亡率,减轻心肌I/RI.     

缺血/再灌注损伤中的心肌细胞凋亡

已知心肌缺血/再灌注引起的心肌细胞死亡包括坏死和凋亡,但由于其触发因素、信号传导通路等的复杂性和 多样性,目前有关心肌细胞凋亡的确切机制尚未明了,其在缺血/再灌注损伤中的意义也较模糊。本文就心肌缺血/再灌注损 伤中心肌细胞凋亡的触发、发生机制、临床意义、检测方法及控制等方面作一简介。     

挥发性麻醉药在减轻缺血/再灌注损伤中的作用

缺血/再灌注损伤是由过量的氧自由基、异常活化的中性粒细胞和许多调理介质释放失调介导的。近年发现挥发性麻醉药抑制缺血/再灌注的氧自由基产生、中性粒细胞粘附及减少某些条理介质的异常释放,从而减轻缺血/再灌注损伤。     

Kupffer细胞在肝移植缺血再灌注损伤中的双重作用

Kupffer细胞足定居于肝内的巨细胞,在月十移植缺血再灌注损伤中发挥着重要的作用,门静脉恢复血流后刺激Kupffer细胞激活,释放活性氧族、多种炎性介质和细胞因子,对肝脏造成损伤.另一方面又可上调HO-1的表达,保护肝脏缺血再灌注损伤,因此,Kupffer细胞在肝移植缺血再灌注损伤中发挥着双重效应.     

缺血预处理在肠缺血/再灌注损伤中的研究进展

缺血预处理是近年来提出的一种新的肠缺血/再灌注损伤的保护方法,即使在小肠长时间缺血/再灌注之前,进行一次或多次短暂的缺血,再灌注过程.研究表明缺血预处理对小肠缺血/再灌注损伤具有保护作用,但机制复杂,尚未明确.现就缺血预处理在肠缺血,再灌注损伤中的研究进展作一综述.     

枯否细胞与肝脏缺血再灌注损伤

休克、肝脏外伤及肝移植所致肝功能衰竭都与肝脏缺血再灌注损伤有关，其中枯否细胞（ＫＣ）的作用不容忽视。ＫＣ可因补体系的激活和钙超载或噬作用而激活，活化后的ＫＣ除主要释放活性氧外，还可入蛋白酶及各种细胞因子，介导对肝细胞的毒性作用，导致严重的肝脏再灌注损伤。干扰ＫＣ功能的药物可能具有重要的临床应用价值。     

Cardioprotective Effect of Succinate Against Ischemia/Reperfusion Injury

(Received for publication on Sept. 12, 1996; accepted on May 12, 1997)     

Protective Effect of Cordycepin on Experimental Testicular Ischemia/Reperfusion Injury in Rats

Objective: To investigate the role of cordycepin in testicular ischemia/reperfusion injury in rats. Materials and methods: Forty Wistar albino rats were randomly divided into four groups, as follows: group one, control (C); group two, torsion and ischemia (I); group three: detorsion with ischemia–reperfusion (IR); and group four, detorsion/cordycepin. The rats were then analyzed macromorphologically and histopathologically, and blood tests were performed. Specifically, the total oxidant status (TOS) and total antioxidant status (TAS) were determined, and malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β levels were analyzed. In addition, pyknotic nuclei, spermatozoa, edema, and hemorrhage were assessed. Results: When the IR and cordycepin groups were compared with the other groups, there was a statistically significant decrease in TNF-α and MDA levels (p < 0.05). Increased TAS levels were observed in the cordycepin group compared with the control group. TOS levels were significantly increased in the I and IR groups, but decreased in the cordycepin group (p < 0.05). Similar effects were observed in tissue biochemistry analysis. Histopathological evaluations revealed that the spermatozoa count was decreased in the I and IR groups. However, there was an increase in the cordycepin group, as well as a statistically significant difference between the IR and cordycepin groups (p < 0.01). Finally, edema and inflammation were increased in the I and IR groups, but decreased in the cordycepin group. Conclusions: Histological and biochemical findings revealed that cordycepin protected against IR-induced testicular injury.     

The Effect of Vitamin E Succinate on Ischemia Reperfusion Injury

Ischemia–reperfusion (I/R) injury is, in part, related to the burst of reactive oxygen species (ROS) generated after reperfusion. Vitamin E has been shown to exert its biological effects as an antioxidant, inhibiting the ROS. In this report, the effect of Vitamin E succinate (VES) on ischemia/reperfusion injury and NF-κB expression was studied in a rat skeletal muscle model during reperfusion following a 4-h ischemic period. The study group consisted of muscle flaps infused with 150 mg/kg of VES given intraperitoneally 1 h post-initiation of ischemia. Muscle viability based on nitroblue tetrazolium staining, edema, and Doppler blood flow was measured in a control and a study group. Muscle samples were analyzed by standard gel shift assay. The VES experimental group showed an increase in muscle viability compared to controls (average of 44.675% versus 31.925%, respectively, p = 0.0415). Blood flow, measured by Doppler 24 h after reperfusion, was increased in the VES study group compared to controls (10.3 vs. 5.1 ml/g/s p = 0.00355). Additionally, the VES group showed a trend of decreasing edema compared with the control; however, not at a level that was statistically significant (p = 0.1267). The VES-treated group showed a decreased expression of NF-κB as compared to controls (p < 0.05). These results show that vitamin E succinate has a protective effect in preventing I/R injury as measured by increased muscle viability and reperfusion blood flow. Vitamin E can exert its efforts as an antioxidant as well as other biological roles, including inhibition of NF-κB.     

Ameliorative Effects of Proanthocyanidin on Renal Ischemia/Reperfusion Injury

Introduction. Several natural products have been reported to have beneficial effects on ischemia/reperfusion (I/R) injury, particularly from a preventative perspective. Therefore, this study was designed to investigate the efficiency of proanthocyanidin (PA), a natural product derived from grape seed, on renal dysfunction and injury induced by I/R of rat kidney. Materials and Methods. Twenty-four male Sprague-Dawley rats were divided into three groups: sham-operated, I/R, I/R+PA. Rats were given PA (100 mg/kg/day peroral) 7 days prior to I/R. All rats except sham-operated underwent 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood were obtained for evaluation. Superoxide dismutase, glutathione peroxidase, malondialdehyde, protein carbonyl content, and nitrite/nitrate level (NO_x) were determined in the renal tissue. Serum creatinine (S_Cr), blood urea nitrogen (BUN), and aspartate aminotransferase (AST) were determined in the blood. Additionally, renal sections were used for histological grade of renal injury. Results. PA significantly reduced the I/R-induced increases in S_Cr, BUN, and AST. In addition, PA markedly reduced elevated oxidative stress product, restored decreased antioxidant enzymes, and attenuated histological alterations. Moreover, PA attenuated the tissue NO_x, levels indicating reduced NO production. Conclusions. The pretreatment of rats with PA reduced the renal dysfunction and morphological changes, ameliorated cellular injury, and restored renal antioxidant enzymes caused by renal I/R.     

miRNAs调控缺血再灌注损伤过程的研究进展

微小RNA(microRNA,miRNA)是一类长度为二十几个核苷酸的内源性非编码调控RNA,通过序列特异性翻译抑制或mRNA裂解来调控基因表达,参与细胞发育、增殖、分化、凋亡等一系列重要生物学进程.近期的研究发现,miRNA在缺血再灌注的发生和发展中起着重要的作用.已发现若干miRNA直接参与肝脏及大脑缺血再灌注的发生和发展.作为一类新的分子靶标,miRNA应用于缺血再灌注的干预及治疗具有广阔的前景.     

Effects of Intravenous Anesthetics on Renal Ischemia/Reperfusion Injury

Background. Renal ischemia/reperfusion (I/R)-induced tubular epithelial cell injury, called ischemic acute renal failure, is associated with high mortality in humans. Protecting the kidney against I/R injury is very important during complicated renal operations, transplantation surgery, and anesthesia. Aim. The purpose of this study was to investigate and compare the efficiency of ketamine, thiopental, propofol, etomidate, and intralipid in reducing the injury induced by free radicals in a rat model of renal I/R. Method. Forty-two Wistar rats were divided into seven groups in our study. Rats in the sham group underwent laparotomy and waited for 120 minutes (min) without ischemia. Rats in the control group were given nothing with ischemia-reperfusion. Rats in the I/R groups were given ketamine (20 mg/kg), thiopental (20 mg/kg) propofol (25 mg/kg), etomidate (10 mg/kg) and 10% intralipid (250 mg/kg) intraperitoneally 15 min prior to the ischemia for 60 min, followed by reperfusion for 60 min. The blood samples and kidney tissues of the rats were obtained under anesthesia at the end of the reperfusion period. Biochemical malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), blood urea nitrogen (BUN), creatine (Cr), aspartate aminotransferase (AST) were determined, and histopathological analysis was performed with these samples. Results. MDA level was increased significantly in the control group (p < 0.05). Histopathological findings of the control group confirmed that there was renal impairment by tubular cell swelling, interstitial edema, medullary congestion, and tubular dilatation. MDA levels were lower in the ketamine, thiopental, and propofol groups compared to the control group (p < 0.05). In the thiopental and propofol groups, the levels of histopathological scores were significantly lower than control and etomidate groups in ischemia-reperfusion. Conclusion. Our results demonstrated that I/R injury was significantly reduced in the presence of propofol and thiopental. The protective effects of these drugs may belong to their antioxidant properties. These results may indicate that propofol and thiopental anesthesia protects against functional, biochemical, and morphological damage better than control in renal I/R injury.     

雌二醇对兔心肌缺血-再灌注损伤的保护作用

目的探讨17b-雌二醇(E2)对兔心肌缺血-再灌注(I/R)损伤的保护作用。方法通过结扎冠状动脉左前降支建立兔在体心肌I/R损伤模型,将36只兔随机分为3组(每组12只),对照组:心肌缺血前静脉注入1ml乙醇;早期组:心肌缺血前注入10μg/kgE2;晚期组:再灌注前注入10μg/kgE2。化学发光法测定E2的浓度,检测血清超氧化物歧化酶(SOD)、丙二醛(MDA)、肌酸激酶同工酶(CK-MB)的变化,称重法测定心肌梗死范围,TUNEL法检测心肌细胞凋亡。结果与对照组比较,早期组和晚期组CK-MB、MDA含量明显降低(P<0.05),SOD活性明显升高(P<0.05),心肌梗死范围及凋亡指数显著降低(P<0.05),但早期组和晚期组之间比较差异无统计学意义。结论E2对减轻心肌I/R损伤的作用是在再灌注过程中,这种作用可能是通过抗氧化、抗凋亡和减少心肌细胞坏死途径实现的。     

Ischemic Preconditioning-Like Effect of Polyunsaturated Fatty Acid-Rich Diet on Hepatic Ischemia/Reperfusion Injury

Aim  

The aim of this study was to investigate a possible preconditioning effect of oral diet enriched with polyunsaturated fatty acids (PUFAs) on liver ischemia/reperfusion (I/R) injuries.