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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 therapeutic effect of silymarin (SIL) combined with praziquantel (PZQ) on liver fibrosis induced by schistosoma japonicum in mice and its mechanism. Methods Fifty Kunming mice were randomly divided into five groups randomly. Kunming mice were infected with Schistosoma japonicum through the application of cercariae of Schistosoma japonicum. A group was blank control group, B group was model control group, C group was PZQ The treatment group (PZQ 500mg / kg body weight after 6 weeks of infection, continuous administration for 2 days), D group was SIL treatment group (started 6 weeks after the start of gavage 100mg / kg body weight, continuous administration for 8 weeks), E group Combination of SIL and PZQ (dosing regimen C + D). After 8 weeks of drug administration, plasma and liver were collected. Liver damage and collagen deposition in mice were observed by HE staining and Masson staining. Plasma ALT and AST levels in mice were measured by Lai’s method and detected by Western blot The expression of TGF-β1 and MMP-2 in rat liver tissue were detected. Results Compared with group B, the liver index, plasma ALT and AST, the expression of TGF-β1 and MMP-2 in C, D and E groups were decreased, the diameter of granuloma and the deposition of collagen fibers were decreased. The index of liver, plasma ALT and AST, the expression of TGF-β1 and MMP-2 in E group were lower than those in C and D group. Conclusion SIL combined with PZQ can synergistically enhance the protective effect against liver fibrosis induced by Schistosoma japonicum. Down-regulation of TGF-β1 and inhibition of hepatic stellate cells (HSCs) activation play a key role in the further development of anti-hepatic fibrosis.