一贯煎对CCl_4诱导肝纤维化大鼠肝细胞凋亡及其调控基因表达的影响  被引量:11

Effect of "Yiguan Decoction" on Hepatocellular Apoptosis and Underlying Gene Expression in CCl_4-induced Hepatic Fibrosis

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作  者:曹健美[1,2] 陶庆[1] 慕永平[1] 冯琴[1] 彭景华[1] 刘平[1,2] 胡义扬[1] 

机构地区:[1]上海中医药大学附属曙光医院肝病研究所,上海201203 [2]上海中医药大学,上海201203

出  处:《上海中医药大学学报》2012年第5期70-75,共6页Academic Journal of Shanghai University of Traditional Chinese Medicine

基  金:国家自然科学基金重大研究计划重点项目(90409020);国家自然科学基金面上项目(30973924);上海市教委创新团队项目(第1期);国家中医药管理局中医肝胆病重点学科项目

摘  要:目的:研究一贯煎对CCl4诱导的大鼠肝纤维化肝细胞凋亡及其调控基因表达的影响。方法:用50%CCl4橄榄油溶液(1 ml/kg)大鼠腹腔注射造模,每周2次,共9w。于造模3w和6w末,随机抽取正常及模型大鼠处死作动态观察。从第7w始模型大鼠随机分为模型对照组和药物干预组,药物干预组给予一贯煎灌胃,共计3w。9w末检测肝组织Fas、Bax、Bcl-xL、细胞色素(Cyt)C、Caspase-12、Caspase-3蛋白表达和肝细胞凋亡情况。结果:①与正常组大鼠比较,3w、6w及9w时模型大鼠肝组织Fas、Bax和Caspase-12蛋白表达逐渐升高(P<0.05,P<0.01)。与9w模型组比较,一贯煎组Fas、Bax和Caspase-12蛋白表达显著降低(P<0.01),而Cyt C和Bcl-xl蛋白表达在各组之间无显著差异(P>0.05)。②与正常组比较,造模3w时肝组织Caspase-3蛋白表达达到高峰(P<0.01),肝细胞凋亡数量亦达到高峰;6w、9w模型组大鼠Caspase-3蛋白表达和肝细胞凋亡较3w有降低的趋势。与9w模型组大鼠比较,一贯煎组大鼠Caspase-3蛋白表达显著降低,肝细胞凋亡显著减少。结论:一贯煎抑制CCl4诱导大鼠肝纤维化肝细胞凋亡的作用机制可能与干预Fas和内质网凋亡通路有关。Objective: To investigate the effects of "Yiguan Decoction" on hcpatocellular apoptosis and underlying gene expression regulation in CC14-induced hepatic fibrosis. Methods: Rats were treated with 50% CCI4 in oil (ip, 1 mg/kg, twice a week) for nine weeks to establish the model. Rats in control group and model group( n =6 ) were sacrificed to observe its pathological condition dynamically after treatment for three weeks and six weeks. Rats were randomly divided into two groups: model group and "Yiguan Decoction" group which was treated with "Yiguan Decoction" for three weeks. After treatment, rats were sacrificed, and the protein expression of Fas, Bax, Bcl-xl, Cytochorome C (Cyto C), Caspase-12 and Caspase-3 and hepatocellular apoptosis in fiver were measured. Results: (1)The protein expression of Fas, Bax and Caspase-12 in rats liver in model group increased gradually compared with control group after treatment for three weeks, six weeks, and nine weeks, respectively( P 〈0.05, P 〈0.01 ). After treatment for nine weeks, the protein expressions of Fas, Bax, and Caspase-12 in "Yignan Decoction" group were reduced significantly compared with model group (P 〈0.01 ). However, there was no significant difference in the protein expression of Cyto C and Bcl-xl between the two groups. (2)The protein expression of Caspase-3 in liver reached a peak, coincident with the amount of hepatocellular apoptosis in model group after treatment with CC14 for three weeks. However, the protein expressions of Caspase-3 and hepatocellular apoptosis in model group tended to decrease after treatment with CC14 for six weeks and nine weeks. Besides, the protein expressions of Caspase-3 and hepatocellular apoptosis in "Yiguan Decoction" group reduced significantly compared with model group after treatment for nine weeks. Conclusion: " Yiguan Decoction" can inhibit hepatic fibrosis and hepatocellulm" apoptosis in CC14-induced rat by reducing Fas expression and influencing end

关 键 词:一贯煎 肝纤维化 细胞凋亡 基因表达 

分 类 号:R285.5[医药卫生—中药学]

 

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