穿心莲内酯调控硫代乙酰胺诱发小鼠肝纤维化的作用机制
Mechanism of andrographolide regulation thioacetamide-induced liver fibrosis in mice
作者:刘志勇;易坚;邹小明;
Author:
收稿日期: 年卷(期)页码:2016,31(04):-368-374
期刊名称:华西药学杂志
Journal Name:WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字:硫代乙酰胺;穿心莲内酯;小鼠;肝纤维化;机制;免疫组织化学染色;双重免疫荧光染色;马森三色染色法
Key words:
基金项目:赣州市指导性科技计划基金资助项目(2010)
中文摘要
目的利用硫代乙酰胺(TAA)诱发小鼠肝纤维化的动物模型,探讨穿心莲内酯(AG)减缓肝纤维化的作用及其分子机制。方法每周给予小鼠2次100 mg·kg~(-1)TAA,分别于第1、4周取样,并同时喂食高(100 mg·kg~(-1))、低(20 mg·kg~(-1))剂量AG,于第4周后取肝脏组织做组织切片、免疫组织化学染色、双重免疫荧光染色,收集血清做丙氨酸氨基转移酶分析。结果AG可降低TAA所诱发肝内炎性物质与过氧化反应的表达,降低肝组织中Neutrophil、CD11b、F4/80的表达以及NF-κB、COX-2、p-c PLA2、Nrf2蛋白质等的表达量,并能调控肝内脂质过氧化作用,上调SMP30蛋白质水平;组织切片染色显示:给予TAA4周后的小鼠肝脏有明显纤维化,而随着给予AG剂量的增加有显著改善作用;随着AG剂量的增加减少了肝脏内α-SMA、TGF-βR1蛋白质的表达量;使用双重免疫荧光染色法发现AG减缓肝纤维化的作用与调控星状细胞活化相关。结论AG能调控肝内炎性病变进而减缓TAA所引起的肝脏纤维化。
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