TGF-β_1和ECM与糖尿病肾病关系的实验研究

A pathological study on the relationship between TGF-β_1、ECM and diabetic nephropathy

目的 观察高糖条件下大鼠肾小球系膜细胞 (GMC)分泌细胞外基质 (ECM)成分中纤粘连蛋白 (FN)、层粘连蛋白 (L AM)、 及 型胶原和转化生长因子 β(TGF- β1 )的变化 ,探讨细胞因子和细胞外基质在糖尿病肾病发病中的作用。方法 采用体外大鼠肾小球系膜细胞培养 ,用 EL ISA方法测定培养上清液中的 ECM和 TGF-β1 。结果 1高糖条件下 ,GMC合成和分泌 TGF-β1 增加。 2高糖对体外培养的系膜细胞分泌 ECM的影响具有选择性 ,仅增加功能相关蛋白的合成 ,而对其它类型的间质胶原没有影响。结论 体外高糖可增加 TGF-β1 和 ECM的合成。由此可以推断 ,在体内肾小球系膜细胞对高血糖的反应是增加 TGF- β1 和 ECM的合成 ,导致糖尿病肾小球硬化。

Objective To observe the effect of high glucose on secretion of transforming growth factor and extracellular matrix of cultured rat glomerular mesangial cells,the level of TGF β 1 、fibronection (FN),laminin (LAM),type Ⅳ collagen and type Ⅲ collagen in the tissue culture supernatant.Methods The culture of rat glomerular mesangial cells was established and the TGF β 1、FN、LAM、type Ⅳ collagen、type Ⅲ collagen were analyzed by a solid phase enzyme linked immunosorbent assay (ELISA).Results ①High concentration of glucose increased TGF β 1 biosynthesis and secretion.②High concentration of glucose selectively affected groups of functionally related proteins.Conclusion In vitro high glucose levels increased mesangial cell synthesis of the ECM and TGF β 1.The present studies suggest that mesangial cells may increase TGF β 1 and ECM synthesis in response to hyperglycemia and that this response could contribute to the accumulation of extracellular matrix responsible for diabetic glomerulosclerosis.