贝前列素钠对高糖条件下大鼠系膜细胞细胞外基质代谢的影响  

Effects of beraprost sodium on extracellular matrix metabolism in cultured rat mesangial cells induced by high glucose

作　　者：张倩[1] 薛耀明[1] 袁园[1] 江颖娟[1] 王玲[1] 

机构地区：[1]南方医科大学南方医院内分泌代谢科,广东广州510515

出　　处：《南方医科大学学报》2013年第12期1819-1822,共4页Journal of Southern Medical University

基　　金：糖尿病防治中心国际合作研究项目粤财工[2010]207号

摘　　要：目的探讨前列环素类似物贝前列素钠(BPS)对高糖条件下大鼠系膜细胞细胞外基质代谢的影响及其可能的机制。方法将实验分为对照(NG)组、高糖(HG)组和高糖联合不同浓度BPS组(0.5、1、2、5μmol/L)。体外培养系膜细胞,收集24、48 h时细胞培养上清液,Elisa法测转化生长因子β1(TGFβ1)、纤维连接蛋白(FN)及基质金属蛋白酶-2(MMP-2)蛋白的表达;提取细胞总蛋白,免疫印迹法测Smad3磷酸化蛋白的表达。结果与NG组相比,HG培养24及48 h细胞TGFβ1、FN蛋白表达均显著增加(P<0.01),MMP-2蛋白表达量显著下降(P<0.01);细胞培养24、48 h后,与HG组相比,HG+1μmol/L BPS组、HG+2μmol/L BPS组及HG+5μmol/LBPS组细胞TGFβ1蛋白表达量均显著降低(P<0.01);HG+2μmol/L BPS组、HG+5μmol/L BPS组细胞FN蛋白表达量均显著降低(P<0.01);HG+2μmol/L BPS组及HG+5μmol/L BPS组细胞MMP-2蛋白表达量均显著增加(P<0.05);HG组细胞Smad3磷酸化蛋白表达较NG组显著增加(P<0.01);与HG组相比,HG+2μmol/L BPS组与HG+5μmol/L BPS组细胞Smad3蛋白磷酸化水平显著下降(P<0.05)。结论 BPS可能通过抑制TGFβ1/Smad3通路活性对高糖条件下系膜细胞ECM代谢起到了保护性的调节作用。Objective To explore effects of beraprost sodium （BPS） on the metabolism of extracellular matrix （ECM） in rat mesangial cells cultured in the presence of high glucose and the possible mechanism. Methods Rat mesangial cells were cultured in the presence of high glucose with or without BPS for 24 or 48 h. The levels of transforming growth factorβ1 （TGFβ1）, fibronectin （FN） and matrix metalloproteinase-2 （MMP-2） protein in the culture supernatants were measured by enzyme-linked immunosorbent assay, and photoshop-Smad3 was detected by Western blotting. Results Compared with the cells in normal glucose, the cells cultured in the presence of high glucose for 24 and 48 h showed significantly increased TGFβ1 and FN protein expression and lowered MMP-2 protein expression （P〈0.01）. Compared with the cells cultured in high glucose, BPS exposure at the concentration of 1, 2, and 5 μmol/L for 24 and 48 h significantly lowered TGFβ1 protein expression （P〈0.01）, and at 2 and 5 μmol/L, BPS significantly decreased FN protein expression and increased MMP-2 protein expression in high glucose-induced cells （P〈0.05）. High glucose exposure also significantly increased the expression phosphorylated Smad3 （P〈0.01）, which was lowered by BPS treatment at 2 and 5μmol/L （P〈0.01）. Conclusion BPS can regulate ECM metabolism in rat mesangial cells cultured in high glucose by inhibiting TGFβ1/Smad3 pathway, suggesting the beneficial effects of BPS in preventing and treating diabetic nephropathy.

关 键 词：贝前列素钠 大鼠系膜细胞 细胞外基质 高糖条件 

分 类 号：R96[医药卫生—药理学]