乌骨藤总皂苷对四氯化碳诱导的雄性大鼠肝纤维化的保护作用  

Protective effects of Saponins from Marsdenia Tenacissima on the CCl_4-induced liver fibrosis in male rats

作　　者：张小磊[1] 苏远[1] 方海明[1] 王佳佳[2] 章礼久[1] 

机构地区：[1]安徽医科大学第二附属医院消化内科,合肥230601 [2]安徽医科大学药理学教研室,合肥230032

出　　处：《中国新药杂志》2017年第9期1047-1052,共6页Chinese Journal of New Drugs

基　　金：安徽省公益性研究联动计划项目(1501ld04046);安徽医科大学校科研基金项目(2015xkj127)

摘　　要：目的:探讨乌骨藤总皂苷(the Saponins of Marsdenia Tenacissima,SMT)对四氯化碳(CCl_4)诱导的大鼠肝纤维化的保护作用及可能机制。方法:将SD大鼠随机分为正常对照组、模型组、SMT给药组(10,20和40 mg·kg^(-1))和秋水仙碱阳性药(0.1 mg·kg^(-1))对照组。通过对大鼠皮下注射CCl_4制备肝纤维化模型,0.3 mL·100 g^(-1),每周2次,共12周。造模4周后给药组分别给予相应剂量的药物灌胃(ig)给药,正常组和模型组ig给予等剂量的0.9%NaCl溶液。12周后处死大鼠,测定肝脾指数;测定血清中HA,LN,CⅣ含量;制备肝脏匀浆,ELISA法测定SOD,GSH-Px活性及HyP,MDA含量;HE,Masson染色观察肝组织病理及胶原沉积变化;免疫组化法检测肝组织α-SMA蛋白表达;Western blot法检测肝组织TGF-β1,Smad7水平。结果:与模型组比较,SMT明显降低肝纤维化大鼠的肝脾指数及HA,LN,CⅣ水平,减少肝组织Hyp,MDA含量,提高SOD及GSH活性,减轻大鼠肝脏病理损伤程度,减少肝组织中α-SMA,TGF-β1的表达,升高Smad7的表达。结论:乌骨藤总皂苷对CCl_4诱导的实验性肝纤维化大鼠有显著的保护作用,其机制可能与抗氧化及抑制TGF-β1/Smad信号通路相关。Objective： To study the protective effects and mechanisms of Saponins from Marsdenia Tenacissima （SMT） on the CC14-induced hepatic fibrosis in male rats. Methods： SD rats were randomly divided into six groups： normal control group, model group, SMT （10, 20, 40mg·kg^-1） groups and positive control group （colchicine 0.1 mg·kg^-1）. Hepatic fibrosis was induced by CCl4 twice a week for 12 weeks. From the 4th week, all the therapeutic groups were treated with the SMT and the colchicine, normal and model rats were treated with equal dosage of saline. At the end of the twelfth week, the liver and spleen index were calculated, the levels of HA, LN, CIV in serum and Hyp, SOD, MDA, GSH-Px in liver tissues were measured. HE and Masson staining were used to evalulate the degree of hepatic fibrosis. The expression of α-SMA in liver tissues was analyzed by immunohistochemistry, and TGF-β1 and Smad7 were detected by Western blot. Results： Compared with the model group, SMT not only reduced the liver and spleen index, the serum contents of HA, LN, CIV and Hyp, MDA in liver tissue, increased SOD and GSH-Px activity, but also improved the morphologic changes of liver fibrosis. Moreover, it obviously decreased the α-SMA, TGF-β1 expression and increased Smad7 tissues. Conclusion： SMT significantly reduces CCl4-induced liver fibrosis in male rats, due to its antioxidant ability and inhibiting TGF-β1/Smad signal transduction pathway.

关 键 词：乌骨藤总皂苷 肝纤维化 抗氧化 TGF-Β1/SMAD信号通路 

分 类 号：R285.5[医药卫生—中药学]