糖化血清蛋白对刺激肾小球系膜细胞表达转移生长因子-β_1的作用

The effect of glycated serum protein on stimulation of trasforming growth factor β1 gene expression in glomerular mesangial cells

目的 探讨Ａｍ ａｄｏｒｉ糖化血清蛋白对肾小球系膜细胞表达转移生长因子－β１（ＴＧＦ－β１）的影响。方法 用体外制备的Ａｍ ａｄｏｒｉ糖化的胎牛血清蛋白（Ａｍ ａｄｏｒｉ－ｍ ｏｄｉｆｉｅｄ ｇｌｙｃａｔｅｄ ｓｅｒｕｍ ｐｒｏｔｅｉｎ）分别在生理浓度葡萄糖（５．５ｍ ｍ ｏｌ／Ｌ）和高浓度葡萄糖（２５ｍｍ ｏｌ／Ｌ）培养液中作用于大鼠肾小球系膜细胞，观察ＴＧＦ－β１ ｍ ＲＮＡ表达有改变。结果 糖化血清蛋白在正常糖浓度下作用于系膜细胞４天后，ＴＧＦ－β１ 基因表达显著增高，为对照组的１．９９倍。结论 糖化血清蛋白对肾小球系膜细胞中的ＴＧＦ－β１基因表达有明显的刺激作用。

Objective To investigate the effect of glycated serum protein on transforming growth factor beta1(TGF β 1) gene expression in cultured glomerular mesangial cells.Methods Rat mesangial cells were cultrued. Glycated serum protein was prepared by incubating sterile filtered normal fetal calf serum for five days at 37℃ with 28 mmol glucose in phosphated buffered saline (PBS). Serum incubated for the same period in PBS without glucose was used as control (normal serum, NS). TGF β 1 mRNA expression was determined in cells incubated in media containing 10% nonglycated or glycated serum (NS or GS), and 5 5 mmol glucose versus 25 mmol glucose for 4 days without passage.Results In cells cultured in 5 5 mmol glucose, the relative ratio for TGF β 1 mRNA level in cells supplemented with GS compared with the level in cells exposed to NS was 1 99. In cells supplemented with NS, the relative ratio for TGF β 1 mRNA level in cells cultured in 25 mmol glucose compared with that in cells cultured in 5 5 mmol glucose was 1 79. Twenty five mmol glucose also augmented the glycated serum induced increase in TGF β 1 mRNA level relative to that observed in 5 5 mmol glucose concentration (Relative ratio of TGF β 1 mRNA level in cells cultured in 25 mmol versus 5 5 mmol glucose:2 42 vs 1 99), giving an additive effect on gene expression of TGF β 1.Conclusion Amadori modified glycated serum protein stimulate mesangial cell TGF β 1 gene expression by mechanisms that were operative under normoglycemic conditions, which would contribute to the development of diabetic nephropathy.