酸敏感离子通道1a在高糖环境下肝纤维化发病中的作用研究  

Effect of ASIC1a on hepatic fibrosis under high glucose

作　　者：王欢[1] 汪应红[1] 田远耀 孙仕伟 黄蒙蒙[1] 李小枫[1] 孟晓明[1] 黄艳[1] 

机构地区：[1]安徽医科大学药学院基础与临床药理教研室安徽医科大学肝病研究所,安徽合肥230032

出　　处：《中国药理学通报》2016年第3期384-389,共6页Chinese Pharmacological Bulletin

基　　金：安徽省学术技术带头人后备人选课题(No 2015H040);安徽省高校优秀青年人才支持计划重点项目资助课题(No gxyq2016049);安徽医科大学临床医学("5+3"一体化)专业学生"早期接触科研"训练计划项目(No 2015-ZQKY-46)

摘　　要：目的研究ASIC1a(acid-sensing ion channel 1a)对糖尿病合并肝纤维化的病理影响及高糖环境下PDGF-BB刺激的HSC-T6细胞活化增殖的作用。方法采用链脲佐菌素(STZ)制备大鼠糖尿病模型,四氯化碳(CCl4)诱导大鼠肝纤维化模型,观察糖尿病组、单纯肝纤维化组及糖尿病并发肝纤维化双模型组肝组织损伤程度及ASIC1a的表达变化;体外实验,利用ASIC1a阻断剂阿米洛利(amiloride)预处理HSC-T6细胞,然后加入高糖处理HSC-T6细胞24 h,再添加重组小鼠血小板衍生生长因子(PDGF-BB)刺激24 h,观察HSC-T6的活化增殖情况;Western blot检测ASIC1a、α-SMA和Collagen I蛋白表达水平。结果 STZ诱导的糖尿病大鼠、CCl4诱导的肝纤维化大鼠和STZ加CCl4联合诱导的糖尿病肝纤维化双模型大鼠肝组织较对照组大鼠肝组织均出现不同程度的肝损伤,其中双模型大鼠的损伤最为严重,且3组大鼠肝组织较对照组大鼠肝组织中ASIC1a表达明显升高,双模型大鼠肝组织中ASIC1a升高最为明显;阿米洛利预处理HSC-T6,明显降低了高糖环境下ASIC1a的表达,并抑制了高糖环境下PDGF-BB诱导的HSC-T6中α-SMA、Collagen I的表达。结论高糖环境加剧CCl4诱导大鼠肝纤维化及PDGF-BB诱导的HSC活化,其可能与高糖环境下ASIC1a的过表达有关。Aim To investigate the effect of ASIC1a(acid-sensing ion channel 1a) on the pathological change of diabetes complication liver fibrosis and the proliferation and activation of hepatic stellate cell(HSC-T6) stimulated by PDGF-BB under hyperglycemia.Methods Diabetes rats model was established by streptozotocin(STZ),and liver fibrosis rats model was induced by carbon tetrachloride(CCl4).Then,the liver extent of damage and the expression of ASIC1 a were observed in the diabetic rats,liver fibrosis rats and diabetes complication liver fibrosis rats.In vitro,after pretreated with amiloride,HSC-T6 was treated with high glucose for 24h and then stimulated with PDGF-BB for another 24 h.The proliferation and activation of HSC-T6 were observed,and the expression of ASIC1 a,α-SMA and collagen Ⅰ were detected by Western blot.Results Compared with the control group,rats from diabetic group induced by STZ,liver fibrosis group induced by CCl4,and the diabetes complication liver fibrosis rats co-induced by STZ and CCl4 were all observed with liver damage at different levels,and tissue injury of complication group was most serious.However,the expression of ASIC1 a in the three model groups was significantly increased compared to the control group.ASIC1 a level was most obvious in the diabetes complication liver fibrosis rats.Amiloride pretreatment significantly decreased ASIC1 a expression and inhibited PDGF-BB mediated proliferation and the expression of α-SMA and collagen Ⅰ in HSC-T6 under high glucose environment.Conclusion High ambient glucose aggravates HSC activation and hepatic fibrosis,and this may be related with the increasing expression of ASIC1 a.

关 键 词：高糖 糖尿病 肝星状细胞 ASIC1a 肝纤维化 活化增殖 

分 类 号：R-332[医药卫生] R322.47