高糖环境下exendin-4对人肾小管上皮细胞CTGF、BMP-7表达的影响

Effect of Exendin-4 on the Expression of Connective Tissue Growth Factor(CTGF) and Bone Morphogenetic Protein-7(BMP-7) in Human Renal Tubular Epithelial Cell Cultured with High Concentration of D-glucose

目的探讨exendin-4对高糖环境下人肾小管上皮细胞(HK-2)结缔组织生长因子(CTGF)、骨形态发生蛋白-7(BMP-7)蛋白和mRNA表达的影响。方法将体外培养的HK-2细胞分为正常糖对照组(NG)、高糖组(HG)、甘露醇组(MG)、高糖+不同浓度的exendin-4组(分别exendin-4 10、20、40pmol/L),于培养48h后,采用免疫细胞化学、RT-PCR方法检测HK-2细胞CTGF、BMP-7蛋白和mRNA表达量。结果与NG相比,HG组HK-2细胞CTGFmRNA和蛋白表达明显升高(P<0.05),BMP-7 mRNA和蛋白表达明显降低(P<0.05),加入exendin-4的各组HK-2细胞CTGF表达较HG组均明显降低(P<0.05),BMP-7的表达较HG组均明显升高(P<0.05)。结论 exendin-4可能会通过抑制高糖环境下HK-2细胞CT-GF高表达,提高BMP-7的表达,改善糖尿病肾病。

Objective To investigate the effect of exendin - 4 on the expression of connective tissue growth factor （CTGF） and bone morphogenctic protein -7 （BMP -7） in human renal tubular epithelial cell cultured in high - glucose environment. Methods HK -2 cells were subcuhured under normal glucose （NG） ,high glucose （HG） , mannitol glucose （MG） and high glucose with different concen- trations of exendin - 4 group （ including exendin - 4 10,20,40pmol/L）. The activity of CTGF and the expressions of BMP - 7 protein and mRNA in cultured HK - 2 cells were detected with immunocytochemistry and RT - PCR at 48h. Results Compared with the normal group, the expression of CTGF significantly increased in the high glucose group （ P 〈 0.05） , the expression of BMP - 7 significantly de- creased in the high glucose group（ P 〈 0.05）. Compared with the high glucose group, the expressions of CTGF was significantly lower in all the exendin - 4 groups（ P 〈 0.05 ） , the expressions of BMP - 7 significantly increased in all the exendin - 4 groups（ P 〈 0.05 ）. Con- clusion Exendin -4 may modulate the process of diabetic nephropathy by inhibiting the expression of CTGF and increasing the expres- sion of BMP - 7 in high glucose - induced HK - 2 cells.