右美托咪定对肠缺血再灌注所致肝损伤的影响

发布时间：2018-03-29 03:06

本文选题：右美托咪定　切入点：肠缺血再灌注　出处：《西南医科大学》2017年硕士论文

【摘要】：目的:研究右美托咪定(dexmedetomidine)对大鼠肠缺血再灌注所致(I/R)肝损伤的保护作用及其机制。方法:清洁级成年健康雄性Dawley-Sprague(SD)大鼠,随机分为4组:假手术组(Sham组)、缺血再灌注组(I/R组)、2.5ug/(kg/h)右美托咪定预处理缺血再灌注组(I/R+DL组)和5ug/(kg/h)右美托咪定预处理缺血再灌注组(I/R+DH组),其中Sham组仅分离肠系膜上动脉(SMA)而不夹闭,开腹90min后关闭腹腔;I/R和右美托咪定处理组采用夹闭SMA 90 min后再灌注的方法制备肠缺血再灌注模型。I/R+DL组和I/R+DH组手术前1h给予尾静脉输注右美托咪定2.5ug/(kg/h)和5ug/(kg/h);I/R组,手术前1小时给尾静脉输注等量的生理盐水。在实施再灌注2小时后,在各组随机抽取8只大鼠,采集肝组织并利用苏木素-伊红染色处理,放置在显微镜下观察肝脏病理结构变化;采用Western bloting检测促凋亡蛋白cleaved caspase 3的表达水平。并利用原位末端脱氧核苷酸转移酶介导的d UTP缺口末端标记法(TUNEL法)检测肝细胞凋亡,然后计算出相应的细胞凋亡指数。测定血清丙氨酸氨基转移酶(alanine Aminotrans ferase,ALT)、门冬氨酸氨基转移酶(Aspartate aminotrans ferase,AST)、乳酸脱氢酶(LDH)白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平;同时检测肝脏活性氧(ROS)、丙二醛(MDA)、超氧化物歧化酶(SOD)及髓过氧化物酶(MPO)活性。结果:与Sham组比较,I/R组、DL组及DH组大鼠肝损伤明显,caspase-3蛋白表达量、凋亡指数、ROS、MDA、IL-6、TNF-α及MPO含量明显增加,而SOD活性减少,差异有统计学意义(P0.05或0.01)。与I/R组比较,DL组及DH组以上指标得到明显改善,差异有统计学意义(P0.05或0.01);与DL组比较,DH组以上指标得到一定程度改善,差异有统计学意义(P0.05或0.01)。结论:1、肠缺血再灌注可以诱发远隔器官肝脏损伤。2、右美托咪定对大鼠肠缺血再灌注所致肝损伤具有保护作用,这种保护效应可能具有剂量依赖性。3、其机制可能与一定程度上抑制炎性反应、氧化应激损伤及肝细胞凋亡有关。
[Abstract]:Aim: to study the protective effect of dexmemedetomidine on hepatic injury induced by intestinal ischemia and reperfusion in rats and its mechanism. They were randomly divided into four groups: sham group (sham group), ischemia reperfusion group (I / R group) 2.5 ugr / kg / h) right metoimidine preconditioning ischemia reperfusion group (I / R DL group) and dexmetomidine preconditioning ischemia reperfusion group (I / R DH group), in which only intestinal system was isolated in Sham group. Superior membranous artery (SMA) without clipping, After opening 90min, I / R and dexmetomidine treatment group were used to make intestinal ischemia reperfusion model by clamping up SMA 90 min and reperfusion. Ir / R DL group and I / R DH group were given caudal vein infusion of dexmetomidine 2.5 ugr / kg / kg 路h / h before operation, and 5 ugr / kg / kg / h / I / R group, respectively. After 2 hours of reperfusion, 8 rats were randomly selected in each group. Liver tissues were collected and treated with hematoxylin-eosin staining. The expression of apoptotic protein cleaved caspase 3 was detected by Western bloting, and the apoptosis of hepatocytes was detected by in situ terminal deoxynucleotidyl transferase-mediated d UTP Nick end labeling (Tunel). Then the corresponding apoptotic index was calculated and the levels of serum alanine Aminotrans ferase (alt), aspartate aminotrans transferase (AST) and tumor necrosis factor- 伪 (TNF- 伪) were measured. The activity of reactive oxygen species (Ros), malondialdehyde (MDA) MDAA, superoxide dismutase (SOD) and myeloperoxidase (MPO) were also detected. Results: compared with Sham group, the expression of caspase-3 protein and the content of TNF- 伪 and MPO were significantly increased in DL-dl group and DH group. Compared with I / R group, the above indexes of DL group and DH group were obviously improved, the difference was statistically significant (P0.05 or 0.01), and the above indexes of DH group were improved to some extent compared with DL group. Conclusion the intestinal ischemia-reperfusion can induce liver injury of distant organs. Dexmetomidine has protective effect on hepatic injury induced by intestinal ischemia-reperfusion in rats. The protective effect may be dose-dependent, and its mechanism may be related to the inhibition of inflammatory response, oxidative stress injury and hepatocyte apoptosis to some extent.
【学位授予单位】：西南医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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