葛根总黄酮对Lieber-Decarli酒精性肝损伤大鼠库普弗细胞活化信号通路的干预作用  

Effects of Pueraria Total Flavones on Activation Signal Pathway of Kupffer Cell in Alcoholic Hepatic Injury Rats Induced by Lieber-Decarli Liquid Diet

作　　者：崔团[1] 彭景华[1] 唐亚军[1] 傅琪琳[1] 许丽莉[1] 冯琴[1] 胡义扬[1,2] 

机构地区：[1]上海中医药大学附属曙光医院肝病研究所肝肾疾病病证教育部重点研究室,上海201203 [2]上海市高校中医内科学E-研究院,上海201203

出　　处：《上海中医药大学学报》2011年第3期71-75,共5页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：上海市教育发展基金会"晨光计划"项目(2007CG56);国家自然科学基金青年基金项目(81001575);上海市教委项目(07cz024);上海高校创新团队(第1期)建设项目

摘　　要：目的:观察葛根总黄酮对Lieber-Decarli酒精性肝损伤大鼠库普弗细胞活化信号通路的干预作用。方法:采用Lieber-Decarli酒精饮料饲养8周诱导的酒精性肝损伤模型,分设无酒精饮料组(C),酒精饮料组(M),酒精饮料+葛根总黄酮低剂量组(LT),酒精饮料+葛根总黄酮高剂量组(HT),每组10只大鼠,造模第3周起分别灌胃给药或蒸馏水至8周末取材。生化检测血清丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)及肝组织谷氨酰转肽酶(GGT)活性,HE染色观察大鼠肝组织病理改变,油红染色观察肝组织脂肪变性情况,免疫组化观察库普弗细胞活化状态,Western-blot方法检测肝组织TNF-α、Toll样受体2(TLR2)、TLR4、CD68蛋白表达。结果:与C组比较,M组大鼠血清ALT、AST活性及肝组织GGT活性明显升高,肝组织CD68、TNF-α、TLR2及TLR4的蛋白表达升高,差异有统计学意义(P<0.01)。与M组比较,HT组和LT组肝组织CD68、TNF-α、TLR2及TLR4的蛋白表达降低,差异有统计学意义(P<0.01);HT组血清ALT、AST活性及肝组织GGT活性降低,差异有统计学意义(P<0.05,P<0.01);LT组肝组织GGT活性降低,差异有统计学意义(P<0.01)。HT组与LT组比较,差异无统计学意义(P>0.05)。结论:葛根总黄酮对Lieber-Decarli酒精饲料诱导的大鼠慢性酒精性肝损伤具有显著的防治作用,该作用可能与其抑制内毒素受体TLR4、TLR2进而抑制库普弗细胞活化有关。To observe the effects of pueraria total flavones on activation signal pathway of Ku pffer cell in alcoholic hepatic injury rats induced by Lieher-Decarli liquid diet. Methods： The alcoholie hepatic injury models were established by Lieber-Decarli liquid diet for 8 weeks. SD male rats were divided into control liquid diet group （C, n = 10）, ethanol liquid diet （M, n = 10） , pueraria total flavone low-dosage group （LT, n = 10） , pueraria total flavone high-dosage group （HT, n = 10）. Rats were administered with corresponding dosage of pueraria total flavones or distilled water via gastrogavage for 6 weeks after administration with ethanol or control liquid diet for 2 weeks respectively. ALT and AST in serum and hepatic GGT were analyzed biochemically. Pathological changes of liver tissues were observed in HE staining section and the hepatic lipid deposition was observed in oil red staining section. Kupffer cell activation was observed by immunohistochemical staining. The rotein expressions of CD68, TNF-α, TLR4 and TLR2 in hepatic tissue were evaiuated with Western-blotting. Results： Compared with group C, the levels of ALT and AST in serum and hepatie GGT increased notably, and the protein expressions of CD68, TNF-α, TLR4 and TLR2 in hepatic tissue increased significantly in group M, with a statistical difference （P 〈 0.01 ）. Compared with group M, the protein expressions of CD68, TNF-c~, TLR4 and TLR2 decreased obviously in group HT and LT （ P 〈 0.01 ） ; the levels of ALT and AST in sennn and hepatic GGT decreased in group HT （ P 〈0.05 ,P 〈0.01 ） ; and the level of GTT in hepatic tissue decreased evidently in group LT （ P 〈0. O1 ）. There were no significant differences between group HT and group LT （ P 〉 0.05 ）. Conclusion ： Pueraria total flavones have significant effects on chronic alcoholic hepatic injury in rats induced by Lieber-Decarli diet, and the mechanisms maybe have relationship with inhibiting TRL4 and TRL2 and further inhibiting the Kupfi^r cel

关 键 词：酒精性肝损伤 库普弗细胞 葛根总黄酮 内毒素受体 肿瘤坏死因子 

分 类 号：R285.5[医药卫生—中药学]