南方医科大学学报

南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (12): 1819-.

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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

张倩，薛耀明，袁园，江颖娟，王玲   

  • 出版日期:2013-12-20 发布日期:2013-12-20

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

  • Online:2013-12-20 Published:2013-12-20

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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、5 μmol/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+1 μmol/L BPS组、HG+2 μmol/L BPS
组及HG+5 μmol/LBPS组细胞TGFβ1蛋白表达量均显著降低（P<0.01）；HG+2 μmol/L BPS组、HG+5 μmol/L BPS组细胞FN蛋
白表达量均显著降低（P<0.01）；HG+2 μmol/L BPS组及HG+5 μmol/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+2 μmol/L BPS组与HG+5 μmol/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。

Abstract: 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 factor β1 (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 5 μmol/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.