Tempo 对肝硬化大鼠肝组织缺血再灌注后肝功能的保护作用及机制

摘要

目的：探讨4-羟基-2．2．6．6-四甲基哌啶（ Tempo）对肝硬化大鼠肝组织缺血再灌注后肝功能的保护作用。方法取90只SD成年大鼠采用传统四氯化碳（ CCL4）法制作肝硬化模型并随机分为假手术组、模型组及治疗组各30只。模型组及治疗组行开腹肝门阻断术（假手术组只暴露肝门，不阻断），肝门阻断后30 min恢复血流。治疗组术前缓慢静脉注射TEMPO 10 mg／100 g（用生理盐水稀释10倍），术后每12 h静注1次；模型组及假手术组术前均缓慢静脉注射与治疗组所用药物等体积的生理盐水，术后每12 h静注1次。术后72 h观察两组肝组织病理学变化、细胞凋亡情况；测定肝组织上清液超氧化物歧化酶（ SOD）、过氧化物酶（ CAT）、谷胱甘肽过氧化物酶（ GSH-Px）活性及丙二醛（ MDA）水平；测定三组肝功能指标。结果治疗组肝组织上清液中SOD、CAT、GSH-Px活性明显高于模型组（P＜0．05），MDA水平明显低于模型组（P＜0．05）；ALT、AST及LDH水平明显低于模型组（P＜0．05）。结论 TEMPO对肝硬化缺血再灌注损伤大鼠的肝功能有保护作用。%Objective To investigate the protection of 4-Hydroxy-2.2.6.6-etram-ethyl-piperidinooxy(TEMPO) for liver function of cirrhotic rat after hepatic porta blocking.Methods The traditional carbon tetrachloride ( CCl4 ) method was used to induce liver cirrhosis in 90 adult rats and then equally divided into three groups, which were control group, model group and treatment group.Rats in model group and treatment group were adopted by open hepatic door and interdict operation to block liver door for 30 minutes and then restore blood flow ( rats in control group were adopted by exposed porta only without block) .Preoperative model group and control group were used normal saline ( as the volume of treatment group use) to intravenous injection slowly before operation and every 12 h after operation.Rats in treatment group were intrave-nous injected TEMPO at 10 mg/100 g (10 times diluted with saline water) before operation and static note once every 12 h after operation.All rats were taking the liver tissue and blood samples after operation 72 hours later.The liver tissue patho-logical changes and cell apoptosis were observed.The level of superoxide dismutase( SOD) , peroxidase ( CAT) ,glutathione peroxidase ( GSH-Px) activity and malondialdehyde ( MDA) of liver tissue clear liquid were tested.The liver function of three groups were tested.Results The SOD, CAT and GSH-Px activity of liver tissue in treatment group significantly higher than the model group(P<0.05).The MDA level in treatment group was significantly lower than model group(P<0.05), while liver function index was significantly lower than model group(P<0.05).Conclusions TEMPO can protect the rat liver function of cirrhotic rat after hepatic porta blocking.