Effect of ASIC1 a on hepatic fibrosis under high glucose
10.3969/j.issn.1001-1978.2016.03.017
- VernacularTitle: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
- Author:
Huan WANG
;
Yinghong WANG
;
Yuanyao TIAN
;
Shiwei SUN
;
Mengmeng HUANG
;
Xiaofeng LI
;
Xiaoming MENG
;
Yan HUANG
- Publication Type:Journal Article
- Keywords:
high glucose;
diabetes;
hepatic stellate cell;
acid-sensing ion channel 1 a;
hepatic fibrosis;
ac-tivation and proliferation
- From:
Chinese Pharmacological Bulletin
2016;32(3):384-389
- CountryChina
- Language:Chinese
-
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.
