白藜芦醇预处理对大鼠肝脏热缺血再灌注损伤的保护作用

Protective effects of resveratrol preconditioning on liver ischemia-reperfusion injury in rats

目的研究白藜芦醇对大鼠肝缺血再灌注损伤的作用。方法清洁健康雄性SD大鼠,随机分为4组,每组15只:假手术组(Ⅰ组)、缺血再灌注组(Ⅱ组)、丹参预处理组(Ⅲ组)、白藜芦醇预处理组(Ⅳ组)。Ⅰ组单纯麻醉和开腹,分离出肝十二指肠韧带,不阻断肝门;Ⅱ组夹闭肝蒂,30min后恢复灌流。开腹前10minⅡ组、III组和Ⅳ组分别自阴茎背静脉注射生理盐水(6mL/kg)、丹参注射液(40mg/kg)、白藜芦醇注射液16mg/kg。再灌注1、6和24h取血测定谷草转氨酶(AST)、谷丙转氨酶(ALT)和γ-谷氨酰转肽酶(GGT)、胆汁酸(TBA)的水平,再灌注6h后观察肝组织病理学的改变,TUNEL法观察胆管内皮细胞凋亡情况。结果Ⅱ组、Ⅲ组和Ⅳ组血清ALT、AST含量明显高于Ⅰ组(P<0.01),Ⅲ、Ⅳ组低于Ⅱ组(P<0.01),III组高于Ⅳ组(P<0.05);Ⅱ、Ⅲ、Ⅳ组胆汁中GGT、TAB含量高于Ⅰ组(P<0.01),Ⅲ、Ⅳ组低于Ⅱ组(P<0.01),Ⅲ组高于Ⅳ组(P<0.05),肝组织病理损害Ⅱ组最重,Ⅲ组次之,Ⅳ组最轻;胆管内皮细胞凋亡Ⅱ组最为严重,Ⅲ组次之,Ⅳ组较Ⅲ组轻。结论白藜芦醇可有效改善缺血再灌注对大鼠肝脏的损伤,减轻胆道内皮细胞的凋亡,其保护作用优于丹参。

Objective To study the protective effects of resveratrol on rats＇ hepatic ischemia reperfusion injury （HIRI）. MethodsHIRI model （Pringle＇ method） was made in rats, which weighted 220～260 g, divided into four groups （n =15） randomLy, sham operation group （Ⅰ）, IR group （Ⅱ）, Radix Salviae Miltiorrhizae （RSM） group （Ⅲ）, resveratrol group （Ⅳ）. The rats were sacrificed at 1 h, 6 h, 24 h after ischemia induced for 30 minutes and followed by reperfusion. The levels of serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT） and bile glutamyl-transferase （GGT） and total acid bile （TAB） were measured.Meanwhile, the pathological changes of liver and biliary system were observed （at the time point of 6 h after reperfusion）. Intrahepatic biliary duct endothelial cell apoptosis was also evaluated with TUNEL technique. ResultsSerum concentrations of AST and ALT in group Ⅱ, Ⅲ and Ⅳ were significantly higher than those in groupⅠ （P〈0.01）, and group Ⅲ and group Ⅳ were significantly lower than group Ⅱ （P〈0.01）, and there was significant difference between group Ⅲ and group Ⅳ （P〈0.05）. Serum concentrations of GGT, TAB in group Ⅱ, Ⅲ, Ⅳ andⅤ were significantly higher than groupⅠ （P〈0.01）, group Ⅲ and Ⅳ were significantly lower group Ⅱ （P〈0.01）, and there was significant difference between group Ⅲ and group Ⅳ （P〈0.05）. The pathologi-cal changes of liver in group Ⅱwas the severest, group Ⅲ slighter than groupⅡ, and group Ⅳ was the slightest. So did biliary duct endothelial cell apoptosis. ConclusionsPretreatment with Danshen and resveratrol could both alleviate IR-induced liver injury, lessen biliary duct endothelial cell apoptosis. Resveratrol pretreatment was better than RSM.