缬沙坦对高糖环境中肾小球系膜细胞Megsin表达的影响

目的观察缬沙坦对高糖环境中小鼠肾小球系膜细胞megsin、p38丝裂原活化蛋白激酶(p38MAPK)信号通路、单核细胞趋化蛋白-1(MCP-1)及细胞间黏附分子-1(ICAM-1)表达的影响,探讨缬沙坦对糖尿病肾病的防治作用。方法高糖环境中培养小鼠肾小球系膜细胞,于培养12 h、24 h、48 h末,应用MTT法检测细胞增殖程度,分别应用免疫细胞化学和Western印迹法检测系膜细胞megsin、p-p38MAPK、MCP-1、ICAM-1蛋白表达水平,酶联免疫吸附法(ELISA)检测细胞培养上清Ⅳ型胶原浓度。结果高糖环境中小鼠肾小球系膜细胞megsin、p-p38MAPK、MCP-1及ICAM-1表达增强,细胞增殖明显,细胞上清液中Ⅳ型胶原浓度升高,缬沙坦干预组上述变化明显减弱。结论缬沙坦可下调megsin、p-p38MAPK、MCP-1及ICAM-1表达,抑制系膜细胞增殖及系膜外基质积聚,发挥其独立于降压之外的肾脏保护作用。

Effects of Valsartan on the expression of megsin in glomerular mesangial cells under high concentration glucose circumstance

This study aimed to observe the effects of Valsartan on the expression of megsin,p38MAPK signaling pathway,monocyte chemoattractant protein-1(MCP-1) and intercellular adhesion molecule-1(ICAM-1) in mouse glomerular mesangial cells under high concentration glucose circumstance and investigate the role of Valsartan in the pathogenesis of diabetic nephropathy.We cultured mouse glomerular mesangial cells and the cell proliferation was measured by MTT at 12,24 and 48 h respectively after culture.The expressions of megsin,p-p38MAPK,MCP-1 and ICAM-1 in mesangial cells were detected by immunocytochemical staining and Western blot,while the concentration of type Ⅳ collagen in supernatant of mesangial cells was measured by ELISA.We found that under high concentration glucose circumstance,the expression of megsin,p-p38MAPK,MCP-1,and ICAM-1 were increased,the concentration of type Ⅳ collagen in the cellular supernatant was increased,and mesangial cell proliferation was enhanced compared with control group(P < 0.05).After treatment with Valsartan,the above changes were weakened.Our results suggested that Valsartan can down-regulate the expressions of megsin,p-p38MAPK,MCP-1 and ICAM-1,even suppress mesangial cell proliferation and mesangial extracellular matrix accumulation,so that play a key role in renal protection beyond down-regulate blood pressure.