中国药理学通报2018，Vol.34Issue(5)：645-650,6.DOI:10.3969/j.issn.1001-1978.2018.05.012
丹皮酚激活CKIP-1对高糖诱导的肾小球系膜细胞纤维化的影响
Paeonol up-regulates CKIP-1 to resist high glucose-induced fibrosis in glomerular mesangial cells
摘要
Abstract
Aim To observe whether paeonol can in-hibit fibronectin (FN) and intercellular cell adhension molecule-1 (ICAM-1) expressions in high glucose (HG)-induced glomerular mesangial cells(GMCs) via up-regulating CKIP-1 and activating the Nrf2 signaling pathway. Methods The effects of paeonol on the ex-pressions of CKIP-1,Nrf2,FN and ICAM-1 were eval-uated in GMCs treated with HG. Small interfering RNA was used to deplete CKIP-1 protein expression, and Western bolt was used to detect the expressions of Nrf2, HO-1 and SOD1. DHE fluorescent probe tech-nique was used to determine intracellular superoxide level. Results The protein levels of CKIP-1 and Nrf2 were elevated by paeonol in HG-treated GMCs. In the meanwhile,the expressions of Nrf2 downstream antiox-idant enzymes, i.e. HO-1 and SOD1, were also up-regulated by paeonol, which was accompanied by re-ductions of superoxide and H2O2levels. Importantly, paeonol reversed the excessive accumulation of FN and ICAM-1 in HG-induced GMCs. si-CKIP-1 decreased the up-regulation of Nrf2,HO-1 and SOD1 expressions during paeonol treatment, which was accompanied by increased superoxide and H2O2levels. Furthermore, si-CKIP-1 reversed the down-regulated levels of FN and ICAM-1 induced by paeonol. Conclusion Pae-onol inhibits the expressions of FN and ICAM-1 in HG-treated GMCs possibly by up-regulating CKIP-1 and activating the Nrf2 signaling pathway.关键词
丹皮酚/高糖/CKIP-1/Nrf2/纤维连接蛋白/肾小球系膜细胞/肾脏纤维化Key words
paeonol/high glucose/CKIP-1/Nrf2/fi-bronectin/glomerular mesangial cells/renal fibrosis分类
医药卫生引用本文复制引用
张蕾,邹叶子,公文艳,陈志泉,黄河清..丹皮酚激活CKIP-1对高糖诱导的肾小球系膜细胞纤维化的影响[J].中国药理学通报,2018,34(5):645-650,6.基金项目
国家自然科学基金资助项目(No 81573477,81770816) （No 81573477,81770816）
广东省自然科学基金重点项目(No 2017A030311036) （No 2017A030311036）
