中国药理学通报2013，Vol.29Issue(5)：723-728,6.DOI:10.3969/j.issn.1001-1978.2013.05.029
黄连素通过S1P2-MAPK信号通路抗糖尿病肾纤维化作用机制研究
Role of berberine in fibronectin expression via S1P2-MAPK signaling pathway in diabetic nephropathy
摘要
Abstract
Aim To investigate the mRNA and protein level of S1 P2 receptor in kidney of alloxan-induced diabetic mice and mesangial cells under high glucose condition treated by berberine, and to explore the role of berberine in S1 P2-mediated fibronectin expression and MAPK signaling pathway. Methods Mice were induced diabetes by intraperitonal injection of alloxan, and randomly divided into normal, diabetes and berberine ( high dose and low dose ) groups. The fasting blood glucose, kidney weight/ body weight, blood urea nitrogen, serum creatinine and urine protein 24 h were measured after 12 weeks. The mRNA and protein level of S1 P2 receptor in kidney of diabetic mice were detected by real-time PCR and western blot analysis, respectively. Protein expression of S1P2 receptor, fibronectin and MAPK phosphorylation in mesangial cells treated by berberine under hyperglycemia condition were measured by western blot analysis. Results In alloxan-induced diabetic mice, berberine signifi-cantly decreased the fasting blood glucose, blood urea nitrogen, serum creatinine and urine protein 24 h, and down-regulated the mRNA and protein levels of S1P2 receptor expression in kidney. In vitro, berberine remarkably decreased the mRNA and protein level of S1P2 receptor and fibronectin expression in mesangial cells cultured under hyperglycemic condition. In addition, phosphorylation of MAPK( ERK1/2, p38MAPK and JNK ) was inhibited by berberine treatment. Conclusion Berberine down-regulates S1P2 receptor expression and abolishes fibronectin expression by inhibiting activation of S1P2-MAPK ( ERK1/2, P38MAPK ) signaling pathway in diabetic condition, which may be one of molecular mechanisms of berberine in diabetic nephropathy treatment.关键词
黄连素/糖尿病肾病/纤维化/1-磷酸鞘氨醇受体/MAPK信号通路/纤维连接蛋白Key words
berberine/ diabetic nephropathy/ fibrosis/ sphingosine-1 -phosphate receptors/ mitogen-activated protein kinase signaling pathway/ fibronectin分类
医药卫生引用本文复制引用
刘慰华,刘世明,林双峰,黄河清..黄连素通过S1P2-MAPK信号通路抗糖尿病肾纤维化作用机制研究[J].中国药理学通报,2013,29(5):723-728,6.基金项目
2012年度高等学校博士学科点专项科研基金(No 20124423120001) （No 20124423120001）
广东省自然科学基金重点项目(No S2012020010991) （No S2012020010991）
广东高校优秀青年创新人才培养计划项目(No 2012LYM_0111) （No 2012LYM_0111）
广州医学院博士、留学归国人员基金项目(No 2011C11) （No 2011C11）
