中国药理学通报2016,Vol.32Issue(3):384-389,6.DOI:10.3969/j.issn.1001-1978.2016.03.017
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 ASIC1 a on hepatic fibrosis under high glucose
摘要
Abstract
Aim To investigate the effect of ASIC1 a ( acid-sensing ion channel 1 a ) 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 hyperglyce-mia. 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 24 h and then stimulated with PDGF-BB for another 24 h. The proliferation and acti-vation of HSC-T6 were observed, and the expression of ASIC1a, 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 com-plication 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 seri-ous. However, the expression of ASIC1a in the three model groups was significantly increased compared to the control group. ASIC1a 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 ofα-SMA and collagenⅠin 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 ASIC1a.关键词
高糖/糖尿病/肝星状细胞/ASIC1a/肝纤维化/活化增殖Key words
high glucose/diabetes/hepatic stellate cell/acid-sensing ion channel 1 a/hepatic fibrosis/ac-tivation and proliferation分类
医药卫生引用本文复制引用
王欢,汪应红,田远耀,孙仕伟,黄蒙蒙,李小枫,孟晓明,黄艳..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[J].中国药理学通报,2016,32(3):384-389,6.基金项目
安徽省学术技术带头人后备人选课题(No 2015H040) (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) ( 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) (“5+3”一体化)