水飞蓟素联合吡喹酮抗小鼠血吸虫病肝纤维化的实验研究  

Studies on the Treatment Effect of Silymarin and Praziquantel against Liver Fibrosis of Schistosomasis Japonicum in Mice

作　　者：张丽君[1] 沈定文[1] 

机构地区：[1]湖北科技学院基础医学院,湖北咸宁457100

出　　处：《时珍国医国药》2016年第2期348-350,共3页Lishizhen Medicine and Materia Medica Research

基　　金：湖北科技学院专项重点课题(No.zx1304)

摘　　要：目的探讨水飞蓟素(SIL)联合吡喹酮(PZQ)抗小鼠血吸虫病肝纤维化的治疗作用及其机制。方法采用日本血吸虫尾蚴敷贴法感染昆明小鼠构建日本血吸虫病肝纤维化模型,昆明小鼠50只随机分为五组,A组为空白对照组,B组为模型对照组,C组为PZQ治疗组(感染6周后PZQ灌胃500mg/kg体重,连续给药2天)、D组为SIL治疗组(感染6周后开始灌胃100mg/kg体重,连续给药8周)、E组为SIL和PZQ联合治疗组(给药方案C+D)。给药干预8周后,收集血浆和肝脏。HE染色和Masson染色观察小鼠肝脏损伤程度和胶原纤维沉积情况,赖氏法检测小鼠血浆丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)含量,Western blot检测小鼠肝组织转移生长因子-β1(TGF-β1)、基质金属蛋白酶2(MMP-2)蛋白表达含量。结果与B组相比较,C、D、E组小鼠肝脏指数、血浆ALT和AST含量、肝组织TGF-β1和MMP-2蛋白表达均降低,肉芽肿直径减小,胶原纤维沉积减少。E组小鼠肝脏指数、血浆ALT和AST含量、肝组织TGF-β1和MMP-2蛋白表达均低于C组和D组。结论 SIL联合PZQ具有协同增强抗小鼠血吸虫病肝纤维化的保护作用,TGF-β1的下调和抑制肝星状细胞(HSCs)的激活在抗肝纤维化的继续发展中起关键作用。Objective To investigate the treatment effects of Silymarin（ SIL） and Praziquantel（ PZQ） against liver fibrosis of Schistosomiasis japonicum and its mechanism. Methods To construct the hepatic fibrosis model of mice with Schistosomiasis japonicum,mice were infected with Schistosomiasis japonicum cercaria using the body immersion method and divided into 5 groups randomly,（ A） control group,（ B） infected but untreated group,（ C） treated with PZQ（ 500 mg / kg） for two consecutive days at the 6 weeks post infection,（ D） treated with SIL（ 100 mg / kg） for 8 weeks at the 6 weeks post infection,（ E） treated with scheme C and D. Mice sera and livers were collected 8 weeks post treatment. Pathological injure and collagen deposition in liver were observed by the HE and Masson trichrome stains. Concentrations of ALT and AST in mice sera were detected using the available commercial kits. TGF- β1 and MMP- 2 in the liver were estimated by western blot. Results Compared with group B,the liver index,ALT and AST in the sera,TGF- β1 and in the liver of group C,D and E mice decreased significantly,diameter of egg granuloma and collagen deposition reduced. The liver index,ALT and AST in the sera,TGF- β1 and in the liver of group E mice were lower than that of group C and D. Conclusion The results indicated that SIL and PZQ could enhance anti- fibrosis protection and might be a promising agent against liver fibrosis of Schistosomiasis japonicum. It might play an important role that SIL and PZQ could decrease TGF- β1 and inhibit the activation of hepatic stellate cells（ HSCs） against liver fibrosis of schistosomiasis japonicum.

关 键 词：水飞蓟素 吡喹酮 血吸虫病 肝纤维化 TGF-Β1 MMP-2 

分 类 号：R383.24[医药卫生—医学寄生虫学]