白芍总苷治疗四氯化碳致大鼠肝纤维化的作用与其影响肝星状细胞功能的关系  

Pharmacological effects of total glucosides from paeony root on CCl_4-induced liver fibrosis and function of hepatic stellate cells

作　　者：李瑞麟[1] 马勇[1,2] 魏伟[1] 叶根深[1] 陈文笔[1,2] 严家春[2] 

机构地区：[1]安徽医科大学临床药理研究所,安徽省高校省级抗炎免疫药理学重点实验室,安徽省中药研究与开发重点实验室,合肥230032 [2]中国人民解放军第123中心医院肝病中心,蚌埠233015

出　　处：《中国新药杂志》2007年第9期685-689,共5页Chinese Journal of New Drugs

基　　金：安徽省2006年度科技攻关计划项目(06013133B);高校博士点基金(20060366003);安徽省科技创新团队基金

摘　　要：目的:研究白芍总苷(TGP)通过影响肝星状细胞(HSC)的功能发挥治疗四氯化碳(CCl_4)致大鼠肝纤维化的作用。方法:建立CCl_4诱导化学性肝纤维化模型,全自动生化仪检测血清中丙氨酸氯基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)水平;放免法检测血清及体外HSC培养上清中透明质酸(HA)和Ⅲ型前胶原(PCⅢ)的含量;流式细胞仪检测HSC凋亡率。苏木素-伊红染色处理肝脏组织切片,光镜观察病理学改变。结果:在CCl_4诱导大鼠肝纤维化模型,TGP给药(40,80,160mg·kg^(-1),ig)均明显降低血清ALT,AST,ALP,HA和PCⅢ水平;升高白蛋白水平及白蛋白球蛋白比值(A/G)。TGP(60,120和240mg·L^(-1))能明显降低HSC体外分泌的HA和PCⅢ水平,促进HSC凋亡,明显改善肝脏病理组织状况。结论:TGP对CCl_4致大鼠肝纤维化具有治疗作用,该作用与其降低HSC分泌HA和PCⅢ、促进HSC凋亡有关。Objective： To study whether total glucosides from paeony root （TGP） improves the function of hepatic stellate cells to treat CC14-induced liver fibrosis. Methods： A model of rat chemical hepatic fibrosis was prepared by subcutaneous injection of carbon tetrachloride （40, 60, 80, 120, 160 or 240 mg·kg^-1 ） into rat liver tissues. The rats＇ serum activities of alanine aminotransferase （ALT） , aspartate aminotransferase （AST） and alkaline phosphatase （ALP） were assayed with HITACHI 7060 automatic biochemistry detection instrument. The rats＇ serum concentrations of hyaluronic and acid （ HA）, procollagen type Ⅲ （PCⅢ） in the cultured hepatic stellate cells （HSC） were determined by a radioimmunoassay. The HSC apoptotic rate was monitored by flow cytometer. The histopathological examination was conducted by sectioning the liver tissues and then staining under a light microscope. Results： TGP （40, 80 and 160 mg·L^-1） significantly decreased the serum levels of ALT, AST, ALP, HA and PCⅢ, increased albumin level and ratio of albumin over globulin （A/G） , and improved the hepatic lesions. TGP（60,120,240 mg·L^-1）significantly decreased the levels of HA and PCⅢ , and escalated the HSC apoptosis. Conclusion.. TGP protected the rat hepatic tissues from CCl4-induced liver fibrosis by reducing HA and PCⅢ levels and escalating HSC apoptosis.

关 键 词：白芍总苷 细胞凋亡 肝星状细胞 肝纤维化 

分 类 号：R965.1[医药卫生—药理学] R975.5[医药卫生—药学]