丹参酮ⅡA减轻肝脏缺血再灌注损伤的作用及分子机制研究  

Effects of Tanshinone ⅡA in Ameliorating Hepatic Ischemia Reperfusion Injury and Its Molecular Mechanisms

作　　者：齐艳艳[1] 史永照[1] 梅怡[1] 冯雯[1] 陈腾[1] 唐剑敏[1] 

机构地区：[1]上海中医药大学附属普陀医院,上海200062

出　　处：《上海中医药大学学报》2011年第2期60-64,F0003,共6页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81072956);上海市科委科研基金资助项目(07JC14067)

摘　　要：目的:研究丹参酮ⅡA(TanshinoneⅡA,TanⅡA)对肝脏缺血再灌注损伤的保护作用及其体内机制。方法:将C57BL/6小鼠随机分为假手术组(A组)、缺血再灌注组(B组)、药物溶媒对照组(C组)及口服TanⅡA不同剂量组(D、E组),治疗组于术前3 d开始TanⅡA灌胃。采用小鼠部分肝叶缺血90min/再灌注模型,再灌注6 h后收集各组小鼠血液及肝脏标本,检测血清中ALT、AST水平,评估肝脏病理损害,Real-time PCR及Western-blot分析肝脏组织HO-1、TLR4的表达及其信号蛋白磷酸化和炎性细胞因子产生的影响。结果:A组小鼠经假手术处理后血清转氨酶(AST和ALT)、IL-6等炎症因子的表达较低,并显示正常的肝脏组织结构;B组小鼠缺血再灌注后,血清转氨酶、IL-6等炎症因子的表达与A组小鼠比较明显升高(P<0.01),肝脏细胞病理损害严重,但与C组小鼠比较,差异无统计学意义。经TanⅡA治疗3 d的D组、E组小鼠血清转氨酶水平较B组、C组明显降低,肝脏的病理损害较轻;肝脏细胞TNF-α、IL-6、IL-1β和MCP-1的表达明显降低;并抑制肝脏细胞TLR4表达以及JNK,p65的磷酸化,促进HO-1的表达,E组的作用较D组更强。结论:TanⅡA预处理能够有效抑制肝脏表达TLR4,并诱导HO-1表达,从而抑制炎症信号的活化,减轻缺血再灌注损伤。Objective ： To study the effects of tanshinone Ⅱ A （ Tan ⅡA） in ameliorating hepatic ischemia reperfusion （IR） injury and its mechanisms in vivo. Methods ： C57 BL/6 Mice were randomized into five groups ： group A that mice received sham operation, group B that mice underwent 90 rain liver lobes ischemia then reperfusion, group C that mice were pretreated with DM- SO before IR operation, group D and E that mice were pretreated with different doses of tanshinone H A three days-before IR operation. The blood and liver samples were collected after 6 hours＇ reperfusion. The levels of ALT and AST were determined to evaluate the pathological injury of liver. The expressions of HO-1 and TLR4, signal protein phosphorylation and inflammatory eytokines in liver were detected by Real-time PCR and Westeru-blot. Results： The levels of ALT, AST and IL-6 in group A were lower and the structure of liver was normal. The levels of ALT, AST and IL-6 in group B increased significantly compared with group A （ P 〈 0. 01 ） and pathological injury of liver was serious. The levels of ALT and AST in group D and E decreased obviously compared with group B and C, and the pathological injury of liver was lighter; the expressions of TNF-α, IL-6, IL-1β and MCP-1 markedly decreased, the expression of TLR4 and the phosphorylation of JNK and p65 were inhibited, the expression of HO-1 was promoted in both group D and E, the effects of group E were more obviously than group D. Conclusion： The pretreatment of Tan H A can inhibit the expression of TLR4 and induce the expression of HO-1, and further inhibit the inflammatory signal activation and alleviate the ischemia reperfusion injury.

关 键 词：丹参酮 缺血再灌注 肝脏 小鼠 

分 类 号：R285.5[医药卫生—中药学]