栀子大黄汤对四氯化碳致小鼠急性肝损伤的保护作用  

Protective Effect of Zhizi Dahuang Tang on Carbon Tetrachloride Induced Acute Hepatic Injury in Mice

作　　者：李伦[1] 钟伟超 梁伟海[1] 陈育尧[1] 黄少慧[1] 吕志平[1] 

机构地区：[1]南方医科大学中医药学院,广州510515

出　　处：《中国实验方剂学杂志》2016年第12期108-112,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金青年基金项目(81302948)

摘　　要：目的:研究栀子大黄汤对四氯化碳(CCl4)所致小鼠急性肝损伤的保护作用,并探讨其作用机制。方法:72只KM小鼠随机分成6组,分别为正常组、模型组、联苯双脂(0.2 mg·kg^(^(-1)))组、栀子大黄汤低、中、高剂量(分别含生药6,12,24 g·kg^(^(-1)))组。小鼠均ig给药,每天1次,连续5 d,末次给药1 h后,除正常组外,其他各组均ip CCl4造成急性肝损伤。采用苏木素-伊红(HE)染色观察肝组织病理变化;检测血清丙氨酸氨基转移酶(ALT),天门冬氨酸氨基转移酶(AST)活性;检测肝组织丙二醛(MDA)水平、超氧化物歧化酶(SOD)活性;蛋白质免疫印迹(Western blot)检测肝组织B淋巴细胞瘤^(-2)蛋白(Bcl^(-2)),Bcl^(-2)相关X蛋白(Bax),剪切的含半胱氨酸的天冬氨酸蛋白水解酶-3(Cleaved-Caspase-3)蛋白表达水平。结果:与正常组比较,模型组小鼠血清ALT,AST活性明显升高(P<0.05),MDA含量升高,SOD活性明显降低(P<0.05),肝细胞变形、坏死程度较为明显,肝组织Bax,Cleaved-Caspase-3表达明显升高,Bcl^(-2)蛋白表达明显降低(P<0.05);与模型组比较,栀子大黄汤各组显著降低血清ALT活性(P<0.05),中、高剂量可显著降低血清AST活性(P<0.05),各组均显著降低MDA含量(P<0.05),提高肝组织SOD活性(P<0.05),肝组织切片表明各用药组能减轻肝细胞变形、坏死程度,以高剂量组最优,栀子大黄汤各剂量均能下调肝组织Bax,Cleaved-Caspase-3表达,上调Bcl^(-2)的表达。结论:栀子大黄汤对CCl4致小鼠急性肝损伤有保护作用,其机制可能与抗脂质过氧化和抑制细胞凋亡有关。Objective： To investigate the protective effect of Zhizi Dahuang Tang（ ZDT） on carbon tetrachloride（ CCl4）-induced acute hepatic injury in mice. Method： A total of 72 KM mice were randomly divided into normal control group,model group,bifendate pill group,ZDT low-dose group,ZDT medium-dose group and ZDT high-dose group,with 12 mice in each group. Bifendate pill（ 0. 2 g·kg-1） or different doses（ 6,12,24 g·kg-1） of ZDT were given to corresponding groups by gavage for consecutively 5 days. The same volume of saline was infused in normal control group and model group. All groups of mice were intraperitoneally（ ip）injected with CCl4,except for normal control group. Mice were sacrificed to collect their blood and liver specimens. Serum alanine aminotransferase（ ALT）, aspartate aminotransferase（ AST）, liver superoxide dismutase（ SOD） and malondialdehyde（ MDA） were detected. Histological examination was performed using hematoxylin-eosin staining and light microscopy, and Bax, Bcl-2 and Cleaved-Caspase-3 were detected for apoptosis by using Western blot. Result： Compared with the normal group,the normal group showed significant increases in serum AST and ALT activities（ P〈0. 05） and MDA content,decreases in SOD activity（ P〈0. 05）,hepatocyte deformation and necrosis,up-regulations in Bax and Cleaved-Caspase-3 expressions and down-regulation of Bcl-2 expression; compared with the model group,ZDT groups showed significant decreases in serum ALT activity（ P〈0. 05）,and ZDT medium and high-dose groups showed significant decreases in serum AST activity（ P〈0. 05）,and all of the groups showed significant reduction in MDA content（ P〈0. 05） and rise in SOD activity（ P〈0. 05）. According to hepatic tissue sections,all of the treatment groups showed alleviations in hepatocyte deformation and necrosis,particularly the high-dose group,and all of ZDT groups showed downregualtions in hepatic tissue Bax,Cleaved-Caspase-3 expression,and up-regulation in Bcl-2. Co

关 键 词：栀子大黄汤 急性肝损伤 四氯化碳 脂质过氧化 凋亡 

分 类 号：R285.5[医药卫生—中药学]