兰州大学机构库 >学院待认领
异丙酚后处理联合缺血后处理对大鼠肝脏缺血再灌注损伤的影响
Alternative TitleEffect of postconditioning with propofol and ischemia on the hepatic ischemia -reperfusion injury in rats
张琰
Thesis Advisor冷玉芳
2010-05-14
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword二异丙酚 再灌注损伤
Abstract目的:探讨异丙酚后处理联合缺血后处理在抑制脂质过氧化反应及抗细胞凋亡方面对大鼠肝脏缺血再灌注损伤的影响。探讨异丙酚后处理联合缺血后处理是否可以加强对缺血再灌注肝脏的保护作用。 方法:健康雄性SD大鼠30只,体重200~250 g,随机分为5组(n=6),参照文献介绍的方法制备肝脏局部缺血再灌注模型。腹腔注射3%戊巴比妥40 mg/kg麻醉后,固定于手术台,常规消毒,腹部正中切口,暴露第一肝门,分离肝十二指肠韧带,用无创血管钳缓慢夹闭供应肝左叶及中叶的肝动脉及门静脉分支1 h,再灌注4 h制备肝脏局部缺血再灌注模型,保留供应肝右叶、尾叶及乳突叶的门静脉分支,防止门静脉及胃肠道淤血。以肝脏表面颜色变灰,质地变软为肝脏缺血成功的标志,待肝脏表面颜色恢复红润为再灌注成功的标志。假手术组(Ⅰ组)仅开腹;缺血再灌注组(Ⅱ组)缺血1h,再灌注4h;缺血后处理组(Ⅲ组)缺血1 h后,再灌注10 s,缺血10 s,重复6次进行缺血后处理;异丙酚后处理组(Ⅳ组)缺血1 h后经尾静脉注射异丙酚10 mg/kg,之后经尾静脉输注异丙酚40 mg? kg-1?h-1,持续1 h;异丙酚后处理+缺血后处理组(Ⅴ组)缺血1 h后进行异丙酚后处理及缺血后处理。于再灌注4 h后测定血清ALT活性、肝组织MDA含量、SOD活性、Bcl-2及Bax的蛋白表达水平,电镜下观察肝细胞超微结构。 结果:与Ⅰ组比较,Ⅱ组~Ⅴ组血清ALT活性及肝组织MDA含量升高,肝组织Bcl-2蛋白表达上调,Ⅲ组~Ⅴ组肝组织SOD 活性升高,Ⅱ组、Ⅲ组及Ⅴ组肝组织Bax蛋白表达上调(P<0.05或P<0.01);与Ⅱ组比较,Ⅲ组~Ⅴ组血清ALT活性及肝组织MDA含量降低,肝组织SOD 活性升高,Bcl-2蛋白表达上调,Bax蛋白表达下调(P<0.05或P<0.01);与Ⅲ组比较,Ⅳ组血清ALT活性及肝组织MDA含量降低(P<0.05或P<0.01)。Ⅲ组~Ⅴ组肝组织病理学改变较Ⅱ组明显减轻。 结论:异丙酚后处理、缺血后处理及异丙酚后处理联合缺血后处理均可减轻肝脏缺血再灌注损伤,其机制可能与抑制肝组织脂质过氧化反应及细胞凋亡有关;异丙酚后处理联合缺血后处理可以通过抑制脂质过氧化反应、上调Bcl-2蛋白的表达和下调Bax蛋白的表达,减轻肝细胞缺血再灌注损伤,但较两组单独后处理方式无明显统计学差异;异丙酚后处理较缺血后处理有更强的抑制脂质过氧化反应。
Other AbstractObjective To investigate the effect of postconditioning with propofol and ischemia on the hepatic ischemia-reperfusion injury at lipid peroxidation and apoptosis in rats. To investigate whether the protection of postconditioning with propofol and ischemia is better than single postcondtioning ways. Methods Thirty male SD rats weighing 200-250 g were randomly divided into 5 groups of 6 animals each: groupⅠsham operation (S); groupⅡ I/R; group Ⅲ ischemic postconditioning (IPC); group Ⅳ propofol postconditioning (PPC) and groupⅤ IPC+PPC. All of these rats anesthetized by intraperitoneal injection 3% sodium pentobarbital (40 mg/kg). Hepatoduodenal ligament was separated after entry into the belly, the first porta hepatis was exposed and a rat local hepatic IRI model was established with reference to the previous method. Blood flow of median and left lobe of the liver was blocked with non-trauma mini artery clamp, causing 70% liver ischemia. However, the blood flow of right lobe was not blocked to prevent blood clot in portal vein and gastrointestinal tract. When the color of liver surface turn gray and the texture turn soft, the model of liver ischemic prepare to succeed. In groupⅡ-Ⅴ the hepatic arteries and veins of middle and left lobes were occluded for 1 h followed by 4 h reperfusion. Ischemia of the liver was confirmed by the color of the liver turning from red to gray. In group Ⅲ and Ⅴ the livers were subjected to six episodes of 10 second ischemia at 10 second intervals at the end of 1 h ischemia before 4 h reperfusion. In group Ⅳ and Ⅴ 0.5 % propofol 10 mg/kg was given iv at the end of ischemia followed by propofol infusion at 40 mg?kg-1?h-1. Blood samples were taken at the end of 4 h reperfusion for determination of serum ALT activity. Mean-while liver specimens were taken for electron microscopic examination and determination of MDA content and SOD activity. Results I/R significantly increased serum ALT activity and MDA content in the liver and decreased liver SOD activity in groupⅡ. The I/R-induced changes were significantly attenuated by propofol and /or ischemic postconditioning in group Ⅲ, Ⅳ and Ⅴ(P<0.05或P<0.01). I/R significantly increased Bcl-2 and Bax protein expression in the liver cells. Propofol and /or ischemic postconditioning increased Bcl-2 protein expression further but decreased Bax protein expression in group Ⅲ, Ⅳ and Ⅴ as compared with groupⅡ(P<0.05或P<0.01). Electron microscopic examination showed ...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/222350
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
张琰. 异丙酚后处理联合缺血后处理对大鼠肝脏缺血再灌注损伤的影响[D]. 兰州. 兰州大学,2010.
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