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Rho激酶抑制剂对部分肝切除大鼠肝缺血再灌注损伤的保护作用 被引量:11

Hepatoprotection of Rho-kinase inhibitor on hepatic ischemia/reperfusion injury in rats with partial hepatectomy
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摘要 目的探讨Rho激酶抑制剂法舒地尔对大鼠部分肝切除肝缺血再灌注损伤(IRI)的保护作用和机制。方法将54只大鼠随机均分为A组(假手术组),B组(I/R模型组),C组(法舒地尔预处理+I/R模型组)。无创伤血管夹阻断肝左、中叶血供45 min(约占全肝的70%)后再灌注,同时切除未阻断的诸肝叶(约占全肝30%)。成模后检测各组术后1,3,6 h各时点血清转氨酶水平,RhoA蛋白的表达,肝组织匀浆中NO和MDA含量及NO,SOD活性,评价Rho激酶抑制剂对肝IRI的保护作用。结果 C组经法舒地尔干预术后,肝功能较B组改善明显,eNOS,SOD活性及NO含量均显著增高,MDA含量降低,SOD/MDA比值增加,病理示肝细胞损伤减轻。RhoA蛋白在A组有一定程度的表达,B组较A组表达增加,C组水平较B组有所减少。结论 RhoA/Rho激酶信号通路在肝IRI过程中起到重要的作用。法舒地尔可抑制RhoA蛋白的表达,调节NO含量,降低肝脏脂质过氧化,促进自由基的清除,从而减少肝脏1/R损伤。 Objective To investigate the protective effect of fasudil,a Rho-kinase inhibitor,on ischemia/reperfusion(I/R) injury after partial liver resection in rats and its mechanisms.Methods Fifty-four Wistar rats were randomly divided into group A(sham operation,control group),group B(I/R group) and group C(fasudil pretreatment + I/R group).I/R models were induced by blocking the blood supply of hepatic left lateral and median lobes(70% blood supply of liver) with an atraumatic microvascular clip for 45 min.After ischemia,the rats were reperfused and the non-ischemic hepatic lobes(30%) were resected at the same time.The serum transaminase,NO and malondialdehyde(MDA) levels,the activity of eNOS and superoxide dismutase(SOD) in liver tissues were determined at 1,3 and 6 h after reperfusion to evaluate the hepatoprotective effects of fasudil.Results The liver function was improved,the SOD activity and NO level was increased,the MDA level was decreased,SOD/MDA ratio was increased and the hepatocytes impairment was alleviated significantly in group C after fasudi pretreatment.RhoA protein showed a basal expressionly in group A.RhoA protein expression significant increased in group B compared with group A,and the elevation was inhibited in group C.Conclusions RhoA/Rho kinase signaling pathway plays an important role in liver ischemia/reperfusion injury.Fasudil inhibits the expression of RhoA protein,regulates NO release,reduces lipid peroxidation in liver tissue and promotes clearance of free radicals.Thus,it protects the liver against 1/R injury.
出处 《中国普通外科杂志》 CAS CSCD 北大核心 2011年第7期720-724,共5页 China Journal of General Surgery
关键词 肝切除术 再灌注损伤 RHOA/RHO激酶 法舒地尔 Hepatectomy Ischemia-Reperfusion Injury RhoA/ROCK Fasudil
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