AGEs/RAGE/SphK1信号通路介导马钱苷抗AGEs损伤GMCs的机制研究

摘要

目的 探讨山茱萸中有效成分马钱苷在缓解晚期糖基化终末产物(AGEs)诱导肾小球系膜细胞(GMCs)损伤的机制.方法 体外培养GMCs,分为空白对照组,模型组(AGEs:200mg/L),马钱苷0.1、1、10μmol/L浓度组.检测细胞增殖率、细胞FN及COL-Ⅳ分泌水平,观察细胞微观结构变化,测定RAGE、SphK1、S1P和TGF-β蛋白表达量.结果 马钱苷可有效抑制AGEs诱导的GMCs增殖,减少FN及COL-Ⅳ分泌,缓解细胞微观结构病变,下调RAGE、SphK1、S1P和TGF-β蛋白表达.结论 马钱苷通过下调AGEs/RAGE/SphK1信号通路,缓解AGEs诱导的GMCs损伤,从而改善糖尿病肾病(DN).%OBJECTIVE To study the mechanism of loganin,the effective componet of Cornus officinalis,on protecting the glomerulus mesangial cell (GMCs) injured by advanced glycation end products (AGEs).METHODS GMCs were divided into control,model (AGEs: 200mg/L),loganin (0.1,1,10μmol/L) groups.The cell proliferation,FN and COL-Ⅳ secretion,microstructure lesions,RAGE,SphK1,S1P and TGF-β protein expressions were measured.RESULTS AGEs induced cell proliferation,FN and COL-Ⅳ secretions,microstructure lesions,RAGE,SphK1,S1P and TGF-β protein expressions were suppressed by loganin.CONCLUSION Loganin can improve the AGEs induced GMCs injury by regulating the AGEs/RAGE/SphK1 signal pathway,and then ameliorate the diabetic nephropathy.