阿托伐他汀钙及缺血后处理对大鼠肝缺血再灌注损伤保护效应的对比研究

The effects of atorvastatin and ischemic postconditioning on hepatic ischemic-reperfusion injury in rats

目的观察大鼠肝缺血再灌注损伤时阿托伐他汀钙与缺血后处理对其保护效应的比较,并探讨其作用机制。方法 28只健康雄性SD大鼠随机分成假手术组(CON)、缺血再灌注组(IR)、缺血后处理组(IP0)、阿托伐他汀钙预处理组(APC),每组7只。建立大鼠70%的在体肝脏缺血再灌注模型,各组于最后灌注后经肝上下腔静脉取血,用于检测血清谷丙转氨酶(ALT)和谷草转氨酶(AST);取肝匀浆低温离心后采用试剂盒测定肝组织中总超氧化物歧化酶(TSOD)、丙二醛(MDA)、髓过氧化物酶(MPO)、一氧化氮(NO)、一氧化氮合酶(NOS)含量变化;同时取肝脏组织作病理切片观察。结果动物模型经持续45min缺血及90min再灌注后,肝功能明显受损,抗氧化酶活力显著下降,肝组织大片坏死;缺血后处理组和阿托伐他汀钙组能明显改善肝IR损伤程度,升高SOD活性,降低MDA、MPO和体内NO的水平,明显减轻肝窦上皮和血管内皮的损伤,减轻肝细胞损伤和炎性细胞的浸润。结论缺血后处理组和阿托伐他汀钙预处理组对大鼠肝缺血再灌注损伤有保护作用且效果相当,而药物处理更简便。其可能的机制为提高机体抗氧化能力、清除氧自由基和抗炎作用有关。

Objective To compare the protective effect of atorvastatinandischemic postconditioning on liver and the possible mechanisms during the hepatic ischemia-reperfusion injury.Methods Twenty-eight healthy male SD rats were randomly divided into 4 groups,namely control group（N）,ischemia-reperfusion group（IR）,ischemic postconditioning group（IPO） and atorvastatin preconditioning group（APC）,each consisting of 7 rats each.Single liver 70% ischemia-reperfusion rats model was established.After the last reperfusion,blood was collected in each group from the superior and inferior vena cava of liver to detect alanine arninotransferase（ALT） and asparate aminotransferase（AST）.Liver homogenate was centrifuged at low temperature,and the content variation of total superoxide dismustase（TSOD）,malondialdehyde（MDA）,myeloperoxidase（MPO）,nitric oxide（NO） and nitrieoxidesynthas（NOS） in liver tissue were measured.Meanwhile,liver tissue section was observed under light microscope.Results After 45 minutes＇ ischemia followed by reperfusion for 90 minutes,it＇s obvious that the normal liver function was impaired,antioxidant enzyme activity decline and the large areas of necrosis in liver tissue were observed.In ischemic postconditioning group and atorvastatin group,the degree of hepatic ischemia-reperfusion injury was significantly reduced while the activity of SOD was increased and the levels of MDA,MPO as well as internal NO were decreased.Meanwhile,the injury of hepatic sinusoid epithelium and vascular endothelial was significantly reduced;so were the injury of liver cells and the Infiltration of Inflammatory cells.Conclusion Both IPO and atorvastatin have similar protective effect on hepatic ischemia-reperfusion injury.Atorvastatin required easier treatments.It＇s possible mechanisms include activating antioxidant free radicals,improving theability of organisms inscavenging oxygen free radicals,and enhancing anti-inflammatory effects.