肝脏肿瘤缺血再灌注损伤后超氧化物歧化酶和丙二醛的改变及意义

目的　探讨缺血再灌注对肿瘤组织的影响及其意义。方法　通过超声引导将VX2肿瘤组织混悬液穿刺注射到新西兰兔肝脏左中叶 ,建立肝脏肿瘤模型 ,用无损伤血管钳阻断肿瘤所在肝叶的肝动脉分支 60min后去除血管阻断恢复血流 ,随机将模型动物分为缺血再灌注前 (对照 )、缺血再灌注后 0min、1h、1d、3d、1周 6个时间组 ,取肝脏组织和肿瘤组织 ,分别测定超氧化物歧化酶 (SOD)和丙二醛 (MDA)的含量。结果　肝脏组织中的SOD含量于缺血再灌注后迅速下降 ,至 0min达最低点 ,随后有所升高 ,至 7d时仍明显低于缺血再灌注前水平 ,各组与对照组对比差异显著 (P <0 .0 0 1) ,而肿瘤组织的SOD含量变化趋势除了 1h达最低点外 ,其余皆与肝脏组织相似 ,各组与对照组对比差异显著 (P<0 .0 0 1) ;肝脏组织的MDA含量于 0min时升至最高 ,随后开始下降 ,至 7d时仍高于缺血再灌注前水平 ,各组与对照组对比差异显著 (P <0 .0 0 1) ,而肿瘤组织的MDA含量于 1h降至最低 ,随后有所升高 ,但至 7d时仍明显低于缺血再灌注前水平 ,各组与对照组比较差异显著 (P <0 .0 0 1)。结论　肿瘤组织缺血再灌注后氧自由基的生成和损伤较正常肝脏组织明显。     

犬小肠缺血再灌注后氧自由基的改变意义

目的研究小肠小范围缺血再灌注后的氧自由基改变及其意义.方法阻断分布于较小范围的小肠动脉,于动脉阻断前、阻断开放后0,30及60min,从与阻断动脉伴行小肠静脉采集血液标本,检测其NO和SOD的浓度结果再灌注后,在0,30及60min的NO浓度分别是(12.1±4.6),(11.6±4.4),(15.5±4.8)μmol.L-1,SOD的浓度分别是(75.0±4.5),(43.4±11.4),(90.3±27.9)×103NU.L-1.NO和SOD的改变特点显示小肠再灌注后其浓度明显低于阻断前(25.6±4.0)μmol.L-1和(169.0±10.8×103NU.L-1,P＜0.01),在再灌注30mm为最底,而至再灌注60min则有明显的升高.结论小范围的小肠缺血再灌注而导致氧自由基升高和小肠损伤,与多脏器和大范围小肠缺血再灌注相比,虽然也很明显,但恢复较快.     

一氧化氮与肢体缺血再灌注后肺损伤

一氧化氮（NO）参与了肢体缺血再灌注后肺损伤，一方面内皮型NO减少参与了肺动脉高压的形成、引起器官的灌注量不足、促进“无复流”现象的发生，另一方面诱导型NO升 高则可能通过降低血管的反应性维持器官的灌注，抗血小板和白细胞聚集，参与中性粒细胞的呼吸爆发，发挥非特异性的免疫功能、清除氧自由基、抑制脂质过氧化等而起代偿性的保护作用。NO生成过多或不足也会对机体产生不利的影响。     

一氧化氮与肢体缺血再灌注后肺损伤

一氧化氮(NO)参与了肢体缺血再灌注后肺损伤,一方面内皮型NO减少参与了肺动脉高压的形成、引起器官的灌注量不足、促进“无复流”现象的发生,另一方面诱导型NO升高则可能通过降低血管的反应性维持器官的灌注,抗血小板和白细胞聚集,参与中性粒细胞的呼吸爆发,发挥非特异性的免疫功能、清除氧自由基、抑制脂质过氧化等而起代偿性的保护作用。NO生成过多或不足也会对机体产生不利的影响。     

肝脏缺血再灌注损伤与钙超载

肝脏缺血再灌注损伤是临床上常见的病理过程,其发生机制与细胞内钙超载有关.钙超载的发生与胞质膜裂隙作用、Na /Ca2 交换、Ca2 -ATP酶活性下降、线粒体功能障碍以及氧自由基有关.钙超载防治措施包括:线粒体ATP敏感的K通道开放剂、麻醉荆、钙离子拮抗剂、线粒体通透性转换孔抑制剂和血红素氧合酶等.     

地塞米松在肝脏缺血再灌注损伤中作用的研究进展

地塞米松(dexamethasone)是人工合成的肾上腺皮质激素,由于其显著的药理作用和廉价易获得的特性成为众多学者研究的热点.故广泛应用于各科治疗多种疾病,是临床常用药物.一氧化氮(nitric oxide,NO)及诱导型一氧化氮台酶(inducible nitric oxide synthase,iNOS)是体内半衰期极短的体液因子,其生物效应广泛.近几年的研究结果表明,NO及iNOS与缺血再灌注损伤关系密切,参与缺血再灌注损伤的发生、发展、预后等多个过程,成为缺血再灌注损伤预处理一个非常重要的研究领域.肝脏缺血再灌注损伤(hepatic ischemia-reperfu-sionin jury,HIRI)是由于需要阻断肝门的肝脏手术、肝脏移植,失血性休克以及晚期脓毒血症等各种原因导致肝血流中断或不足使肝脏缺血,当恢复血供再灌注后,肝细胞功能代谢障碍及结构破坏反而加重,器官功能进一步恶化的现象.     

缺血后处理对肝脏缺血再灌注的保护机制研究进展

肝脏移植是治疗终末期肝病的唯一有效手段,缺血再灌注损伤是移植肝功能受损乃至丧失的主要因素之一.缺血后处理是在组织器官长时间缺血后再灌注早期,对组织器官进行数次短暂的再灌注/阻断的处理方法.众多研究显示,缺血后处理对肝脏缺血再灌注损伤有保护作用.他发挥作用的可能机制,主要是通过对氧自由基、钙超载、中性粒细胞、细胞因子、细胞凋亡、线粒体等几个方面的作用来实现.     

一氧化氮与肺缺血再灌注损伤的研究进展

一氧化氮（nitricoxide，NO）是一种活性很强的自由基，具有广泛的生物学活性。多项研究提示NO在急性肺缺血／再灌注（ischemia／reperfusion，I／R）损伤中具有重要作用。本文重点描述有关一氧化氮在肺I／R损伤中作用的研究进展。     

预处理对肝脏再灌注损伤大鼠肝组织、血液中NO和ET的影响及意义

目的　探讨预处理对肝脏缺血再灌注损伤大鼠肝组织和血液中一氧化氮 (NO)和内皮素 (ET)含量的影响及意义。方法　建立肝脏 70 %缺血再灌注损伤大鼠模型 ,分为对照组、缺血组、缺血预处理组、L -精氨酸组(L - arg)、Nω-硝基 - N -精氨酸甲酯 (L - NAME)组 ,观察各组肝功能变化 ,检测肝组织和血清中 NO和 ET及透明质酸 (HA)水平。结果　预处理可减轻 NO水平的下降和血浆 ET的升高 ,防止肝功酶的升高 (P<0 .0 5 )。结论　预处理可诱导缺血再灌注损伤大鼠 NO产生增加、ET产生减少 ,进而改善其微循环 ,减少再灌注损伤。     

老年高血压患者SOD及血清NO水平的变化

目的通过对３９例老年高血压患者超氧化物歧化酶（ＳＯＤ）活性及血清一氧化氮（ＮＯ）含量的测定，进一步了解高血压与ＮＯ及氧自由基的关系。方法对３９例老年高血压患者，男２４例，女１５例，用比色法测定其ＮＯ含量，用邻苯三酚自氧化法测定ＳＯＤ活性。结果正常对照组ＮＯ含量为７８．１±２２．９μｍｏｌ／Ｌ，ＳＯＤ活性为２７６．４±５７．３Ｕ／Ｌ，老年高血压组ＮＯ含量为５１．８±２０．７μｍｏｌ／Ｌ，ＳＯＤ活性为１６７．４±５２．８Ｕ／Ｌ。高血压组与正常对照组相比，血清ＮＯ含量显著下降（Ｐ＜０．０１），ＳＯＤ活性显著下降（Ｐ＜０．０１），且随病情的加重而下降。结论提示ＮＯ对高血压有防护作用，而ＳＯＤ能增强ＮＯ的防护作用。     

Prophylaxis with carnosol attenuates liver injury induced by intestinal ischemia/reperfusion

AIM： To investigate the possible protective effects of carnosol on liver injury induced by intestinal ischemia reperfusion （I/R）.
METHODS： Rats were divided randomly into three experimental groups： sham, intestinal I/R and carnosol treatment （n = 18 each）. The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h. In the carnosol treatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg carnosol 1 h before the operation. At 2, 4 and 6 h after reperfusion, rats were killed and blood, intestine and liver tissue samples were obtained. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase （AST）, alanine aminotransferase （ALT） and interleukin （IL）-6 were measured. Liver tissue superoxide dismutase （SOD） and myeloperoxidase （IvIPO） activity were assayed. The liver intercellular adhesion molecule-1 （ICAM-1） and nuclear factor κB （NF-κB） were determined by immunohistochemical analysis and western blot analysis.
RESULTS： Intestinal I/R induced intestine and liver injury, characterized by histological changes, as well as a significant increase in serum AST and ALT levels. The activity of SOD in the liver tissue decreased after I/R, which was enhanced by carnosol pretreatment. In addition, compared with the control group, carnosol markedly reduced liver tissue MPO activity and serum IL-6 level, which was in parallel with the decreased level of liver ICAI-1 and NF-κB expression.
CONCLUSION： Our results indicate that carnosol pretreatment attenuates liver injury induced by intestinal I/R, attributable to the antioxidant effect and inhibition of the NF-κB pathway.     

L-nitro-arginine inhibits increase in endothelin binding sites induced by ischemia and reperfusion

We have demonstrated that ischemia and reperfusion promoted augmented contractile response to endothelin-1 (ET) in coronary arteries in the presence of polymorphonuclear leukocytes (PMN). It has been also reported that ischemia and reperfusion increase ET binding sites in cardiac membrane in isolated rat heart perfused by blood cell-free system. To determine the role of PMN and L-arginine to nitric oxide (NO) pathway in these phenomena, isolated perfused rabbit hearts were subjected to 30 min of global ischemia followed by 30 min of reflow in the absence or presence of PMN and 10(-5)M of L-nitro-arginine (LNA). PMN was prepared with Percoll density gradients from peritoneal exudate elicited by glycogen. PMN activated with 10(-6)M of phorbol myristate acetate or their supernatant were infused into the coronary perfusion circuit after 5 min of reflow. LNA was added to perfusate also after reflow. The effect of superoxide dismutase (SOD: 50 IU/ml) was also determined. After the end of protocols, membrane fraction was isolated from the hearts for (125)I-ET-1 binding assay. ET-1 binding (Bmax) showed a significant increase by ischemia and reperfusion (P<0.01 vs control). That was markedly augmented with addition of activated PMN or their supernatant (both P<0.01), but abolished either by LNA or SOD (P<0.01 and P<0.05, respectively). These results indicate that increase in ET-receptor by ischemia and reperfusion is mediated by free radicals generated via L-arginine to NO pathway.     

Inhibition of nitric oxide synthesis increases apoptotic cardiomyocyte death and myocardial angiotensin-converting enzyme gene expression in ischemia/reperfusion-injured myocardium of rats

Cardiomyocyte apoptosis is an important pathogenic mechanism in myocardial ischemia/reperfusion (I/R) injury. It has been shown that nitric oxide (NO) and the renin–angiotensin system (RAS) are closely related, and both systems regulate apoptotic cell death. However, the effects of NO modulation on myocardial apoptotic cell death and changes in the RAS in the I/R-injured myocardium have not been studied. Female Sprague–Dawley rats were randomized into three groups: NO synthesis inhibitor, N^G-nitro-l-arginine-methyl ester (l-NAME, 10 mg/kg); NO precursor, l-arginine (540 mg/kg); and vehicle. The rats were then subjected to 45 min coronary occlusion followed by 4 h reperfusion. The TdT-mediated in situ nick and labeling (TUNEL) indices were 39.9% ± 0.8% at the border and 30.9% ± 1.2% at the center of the I/R area in the vehicle group. L-NAME administration significantly increased these TUNEL-positive cells to 45.3% ± 1.9% and 37.9% ± 1.3%, respectively (P < 0.05 each). L-arginine administration reduced the TUNEL index at the border zone with marginal significance (P = 0.08 vs vehicle group). I/R injury significantly reduced the angiotensin-converting enzyme (ACE) mRNA expression in the left (ventricular) free wall of vehicle group rats. However, ACE mRNA expression was 1.9 times greater in the L-NAME group than that in the vehicle group (P < 0.05). This study showed that the inhibition of NO synthesis increased apoptotic cardiomyocyte death and local ACE mRNA expression in the I/R-injured myocardium. Our observations indicate that NO, ACE, and apoptotic cardiomyocyte death are related to each other during I/R injury. Received: July 9, 2001 / Accepted: August 17, 2001     

左旋精氨酸对家兔心肌缺血再灌注损伤的保护作用

目的探讨左旋精氨酸（Ｌ－Ａｒｇ）对心肌缺血再灌注损伤（ＭＩＲＩ）的保护作用。方法制备家兔ＭＩＲＩ模型,观察Ｌ－Ａｒｇ对血清中和心肌组织中一氧化氮代谢产物（ＮＯＰ）含量、乳酸脱氢酶（ＬＤＨ）活性及心肌细胞形态学变化的影响。结果Ｌ－Ａｒｇ保护组和非保护组比较,血清及心肌ＮＯＰ明显升高（Ｐ＜０．０５）;心肌ＬＤＨ显著增高（Ｐ＜０．０５）,而血清ＬＤＨ无明显变化;心肌细胞形态学异常改变明显减轻。结论Ｌ－Ａｒｇ通过提高机体一氧化氮水平而保护缺血再灌注损伤的心肌。     

Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver

AIM： To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. METHODS： Thirty rats were divided into three groups as sham （Group 1）, control （Group 2）, and Nigella sativa （NS） treatment group （Group 3）. All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS （0.2 mL/kg） intraperitoneally, before ischemia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrifi ced. Serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, and lactate dehydrogenase （LDH） levels were determined. Total antioxidant capacity （TAC）, catalase （CAT）, total oxidative status （TOS）, oxidative stress index （OSI） and my-eloperoxidase （MPO） in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. RESULTS： The levels of liver enzymes in group 3 weresignifi cantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were signifi cantly lower in group 3 than the group 2. Histological tissue damage was milder in the NS treatment group than that in the control group. CONCLUSION： Our results suggest that Nigella sativa treatment protects the rat liver against to hepatic ischemia-reperfusion injury.     

磁化冠状动脉内支架置入术后冠状静脉窦血管活性物质的动态变化及作用机制研究

目的 探讨冠心病患冠状动脉（冠脉）内磁化支架置入术后冠状静脉窦血中一氧化氮（NO），内皮素-1（ET-1）及超氧化物歧化酶（SOD）等血管活性物质的动态变化及作用机制。方法 39例心绞痛患者分为磁化支架（MS）组23例，非磁化支架（NMS）组16例，各例于PTCA术球囊首次扩张前，以及术后的即刻，1小时，3小时，6小时取冠状静脉窦血，测定血清NO），血浆ET-1及SOD。结果 MS组术后6小时内冠状静脉窦血中ET-1水平的变化不如NMS组明显，MS组NO含量较NMS组显著自欺欺人或高，MS组SOD较NMS组升高，结论 （1）MS明显减少术中ET-1释放与术后合成，（2）MS明显增加术后NO生成的速度和量。（3）MS使SOD活力增强，有利于清除活性氧介质，减轻支架置入后缺血/再灌注造成的损伤。     

急性心肌梗死患者溶栓后内皮损伤与神经肽Y、一氧化氮、超氧化物歧化酶、丙二醛的关系

目的探讨急性心肌梗死(AMI)患者溶栓前后血清神经肽Y(NPY)、一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量变化及临床意义.方法测定38例健康人和60例AMI患者溶栓前及溶栓后1、2、3、24、48和72 h血清中NPY、NO、SOD和MDA的含量.结果与健康人比较,溶栓前患者NPY和MDA含量升高,NO和SOD含量降低(P＜0.05).溶栓后1～3 h的再通组与溶栓前及未通组比较,NPY和MDA含量更高,而NO和SOD含量更低(P＜0.01).再通组的NPY和MDA高峰出现在溶栓后2h,而NO和SOD的低谷恰好也出现在溶栓后2h.溶栓24h后再通组NPY和MDA含量下降,而NO和SOD含量升高(P＜0.05),其变化幅度大于未通组(P＜0.01).结论AMI后溶栓1～3 h内NPY和MDA明显升高,NO和SOD明显下降,可能参与溶栓后早期内皮功能损伤.     

急性心肌梗死患者溶栓后神经肽Y、一氧化氮、超氧化物歧化酶、丙二醛含量变化及其临床意义

目的探讨急性心肌梗死(AMI)患者溶栓前后血清神经肽Y(NPY)、一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量变化及临床意义。方法测定108例健康人和171例AMI患者溶栓前及溶栓后1、2、3、24、48和72h血清中NPY、NO、SOD和MDA的含量。结果与健康人比较,溶栓前患者NPY和MDA含量升高,NO和SOD含量降低(P<0.05)。溶栓后1～3h的再通组与溶栓前及未通组比较,NPY和MDA含量更高,而NO和SOD含量更低(P<0.01)。再通组的NPY和MDA高峰出现在溶栓后2h,而NO和SOD的低谷恰好也出现在溶栓后2h。溶栓24h后再通组NPY和MDA含量下降,而NO和SOD含量升高(P<0.05),其变化幅度大于未通组(P<0.01)。结论AMI后溶栓1～3h内NPY和MDA明显升高,NO和SOD明显下降,可能参与溶栓后早期内皮功能损伤。