虫草菌丝水煎液及其有效组分C12对肝纤维化大鼠HGF-α及肝细胞凋亡的影响  

Effects of CsB and its Effective Components on HGF-α and Hepatocytes Apoptosis at Fibrotic Liver in Rats

作　　者：李风华[1] 刘平[2] 王春树[2] 张幸[1] 

机构地区：[1]上海中医药大学科技实验中心,上海201203 [2]上海中医药大学肝肾疾病病证教育部重点实验室,上海201203

出　　处：《中国实验方剂学杂志》2013年第14期271-275,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：上海市科委自然科学基金(12ZR1431700);上海市教育委员预算内科研项目(2010JW25);上海市教育委员会E研究院建设计划项目(E03008);上海市医学领军人才项目(2007A卫01);上海市卫生局中医药科研基金(2012J007A)

摘　　要：目的:研究虫草菌丝治疗二甲基亚硝胺(DMN)模型大鼠肝纤维化有效组分及其作用机制。方法:大鼠ip 0.5%DMN 5 mg.kg-1,每周连续3 d,共4周。造模结束后,模型大鼠随机分组,治疗组分别以虫草菌丝水煎液(CsB)及其组分(C12)以生药800 mg.kg-1ig,每日1次,共2周;正常组及模型组以等量生理盐水ig。疗程结束后,分别检测血清丙氨酸转氨酶(ALT)及天冬氨酸转氨酶(AST),血清白蛋白(Alb)及血清总胆红素(TBiL)含量,检测肝组织羟脯氨酸(Hyp)含量、观察肝组织病理及胶原沉积变化,Western印迹法检测肝细胞生长因子α(HGF-α)的表达,TUNEL染色检测大鼠肝细胞凋亡并计算凋亡数量。结果:与6周模型组比较,CsB及C12治疗组大鼠血清ALT,AST活性、TBil含量和大鼠肝组织Hyp含量显著降低,Alb含量显著升高(P<0.05)。与6周模型组比较,CsB及C12治疗组的坏死出血、炎性细胞浸润、胶原增生、纤维间隔形成有所改善。与模型组比较,CsB及C12治疗组大鼠肝组织的蛋白表达量显著升高(P<0.01)。与6周模型组比较,CsB及C12治疗组大鼠肝细胞凋亡数量显著降低(P<0.01)。结论:CsB及C12能够显著改善肝功能,有显著抗肝纤维化作用。CsB和C12能促进HGF-α表达,抑肝细胞凋亡,使肝细胞凋亡和增殖达到平衡状态,阻断和逆转肝纤维化。Objective： To study the effect and mechanism of CsB and its effective components on liver fibrosis in rats induced by dimethylnitrosamine（DMN）.Method： From the 1st to 4th week,rats were treated with intraperitoneal injection of DMN（5 mg.kg-1） for three continuous day each week.After modeling,normal group and model group were given saline（10 mL.kg-1） intragastrically,and rats in drug treatment group were treated separately with CsB and its components C12（800 mg.kg-1.d-1and 5 mg.kg-1.d-1） for 2 weeks.After all courses of treatment,all rats were sacrificed to harvest blood and liver tissue sample.Serum alanine aminotransferase（ALT）,aspartate transferase（AST）,albumin（Alb）,total bilirubin（TBil） and content of hydroxyproline（Hyp） in liver tissue were detected.Histological changes with HE staining and collagen deposition with sirus red staining in rat liver tissue were observed.Expression of hepatocyte growth factor（HGF-α） and tumor necrosis factor-α（TNF-α） were detected immunohistologically.Result： Compared with 6 weeks model group,serum ALT and AST activity,TBil content and Hyp content in liver tissue in CsB and C12 group lowered and Alb content increased significantly（P 0.05）.Compared with 6 weeks model group,some histological improvement was made in CsB and C12 group.Compared with the 6 wk model group,HGF-α protein expression in liver tissue in CsB and C12 group increased significantly（P 0.01）.Compared with 6 weeks model group,quantity apoptotic hepatocytes in Cs and C12 group decreased obviously（P 0.01）.Conclusion： CsB and C12 can block development and formation of liver fibrosis induced by dimethylnitrosamine,by protecting hepatocytes to resist liver injury,decreasing synthesis of collagen,inhibiting oxidative stress.CsB and C12 can improve the level of expression of HGF-α and inhibit hepatocytes apoptosis to balance apoptosis and proliferation,so as to block or reverse development liver fibrosis.

关 键 词：肝纤维化 虫草菌丝 有效组分 肝细胞生长因子 肝细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]