环杷明抑制肝星形细胞激活改善肝纤维化作用实验研究  

Effect of cyclopamine on inhibiting the activation of hepatic astrocyte and improving hepatic fibrosis

作　　者：刘翔宇 王凌云 LIU Xiangyu;WANG Lingyun(Department of Gastroenterology,First People’s Hospital of Jining,Shandong Province,Jining 272000)

机构地区：[1]山东省济宁市第一人民医院消化内科,济宁272000

出　　处：《陕西医学杂志》2020年第6期663-666,共4页Shaanxi Medical Journal

基　　金：山东省医药卫生科技发展项目(2017WS518);山东省济宁市科技发展计划项目(2014JNJC13)。

摘　　要：目的:探讨环杷明及维生素D3、白藜芦醇、姜黄素在改善肝纤维化中的作用效果并揭示相关机制。方法:构建CCl4诱导的肝纤维化小鼠模型,1个月后进行药物干预,分对照组和肝纤维化组,其中肝纤维化组又分为PBS治疗组、环杷明皮下注射组[5 mg/(kg·d)和10 mg/(kg·d)]、维生素D3皮下注射组[3 ng/(100g·d)]、白藜芦醇灌胃组[200 mg/(kg·d)]、姜黄素灌胃组[400 mg/(kg·d)],连续给药4周后处死小鼠。免疫组化检测小鼠肝损伤、纤维化、血管化。Western blot对肝纤维化[细胞外基质(ECM)积累情况]和星状胶质细胞激活相关蛋白进行检测。结果:环杷明、维生素D3、白藜芦醇、姜黄素等治疗后均可抑制ALT和AST表达(P<0.001),改善纤维化。环杷明组可显著抑制肝组织中CD31、α-SMA表达,且环杷明10 mg/kg浓度治疗效果好于5 mg/kg(P<0.001)。环杷明组可抑制肝组织中α-SMA、CollagenⅠ和TGF-β1表达,且环杷明10 mg/kg浓度治疗效果好于5 mg/kg。结论:环杷明、维生素D3、白藜芦醇和姜黄素均可降低转氨酶水平,抑制肝组织纤维化。环杷明可通过抑制抑制肝星状细胞激活、ECM和血管活化来改善肝纤维化,高剂量组效果更为显著。Objective:To investigate the effect of cyclopa mine,vitamin D3,resveratrol and curcumin on the improvement of liver fibrosis,and to reveal the related mechanism.Methods:The mice model of liver fibrosis induced by CCl4 was established.One month later,drug intervention was performed,and the mice were divided into control group and liver fibrosis group.The liver fibrosis group was divided into PBS treatment group,cyclopa mine subcutaneous injection group [5 mg/(kg·d) and 10 mg/(kg·d)],vitamin D3 subcutaneous injection group [3 ng/(100 g·d)],resveratrol intragastric injection group [200 mg/(kg·d)],curcumin intragastric injection group [400 mg/(kg·d)].The mice were killed after 4 weeks of continuous ad ministration.Immunohistochemistry was used to detect liver injury,fibrosis and vascularization in mice.Western blot was used to detect liver fibrosis [accumulation of extracellular matrix(ECM)]and activation of related proteins in astrocytes.Results:The expression of ALT and AST could be inhibited and the fibrosis could be improved after the treatment of cyclopa mine,vitamin D3,resveratrol and curcumin(P<0.001).The expression of CD31 and α-SMA in liver tissue was significantly inhibited in the cyclopamine subcutaneous injection group,and the therapeutic effect of 10 mg/kg of cyclopa mine was better than that of 5 mg/kg(P<0.001).The expression of α-SMA,collagen Ⅰ and TGF-β1 in liver tissue was inhibited in cyclopa mine subcutaneous injection group,and the therapeutic effect of cyclopa mine 10 mg/kg was better than that of 5 mg/kg.Conclusion:Cyclopa mine,vitamin D3,resveratrol and curcumin can reduce transa minase level and inhibit liver fibrosis.Cyclopa mine can improve hepatic fibrosis by inhibiting hepatic astrocytes activation,ECM and blood vessels activation,especially in the high dose group.

关 键 词：环杷明 肝星状细胞 肝纤维化 动物模型 HH信号通路 小鼠 

分 类 号：R392.5[医药卫生—免疫学]