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目的观察骨形态发生蛋白-7(BMP-7)、转化生长因子-β1(TGF-β1)在尿毒症大鼠肾小球中的表达及活性维生素D对二者表达的影响,探讨维生素D的肾保护作用及机制。方法切除大鼠右肾并结扎左肾动脉前支诱导尿毒症大鼠模型,将尿毒症大鼠分为尿毒症组(UC组)和尿毒症+1,25(OH)2D3组(UD组)。正常大鼠为正常对照组(NC组)。实验第8周,检测大鼠收缩压(SBP),24 h尿蛋白(24 h UP)、尿足细胞(UPC),血清钙、磷、25(OH)D3、成纤维细胞生长因子23(FGF23)水平。反转录(RT)-PCR检测其肾小球BMP-7、TGF-β1 mRNA的表达,蛋白印迹法检测其肾小球BMP-7、TGF-β1蛋白表达。结果 UC组和UD组SBP比较无统计学差异,且均高于NC组。与NC组比较,UC组血清磷、FGF23、24 h UP、UPC显著升高,钙、25(OH)D3降低。与UC组比较,UD组血清磷、FGF23、24 h UP、UPC显著降低,血清钙、25(OH)D3升高。与NC组比较,UC组BMP-7 mRNA及蛋白质的表达明显下调、TGF-β1 mRNA及蛋白质表达明显上调。与UC组比较,UD组BMP-7 mRNA及蛋白质表达分别增加14.8%、31.1%,TGF-β1mRNA及蛋白质表达分别减少35.7%、43.9%。结论 1,25(OH)2D3不仅可改善尿毒症大鼠钙磷代谢,并可增加BMP-7表达,减少TGF-β1表达,减轻蛋白尿及UPC的排泄。
Objective To observe the expression of bone morphogenetic protein-7 (BMP-7) and transforming growth factor-β1 (TGF-β1) in glomeruli of uremic rats and the effect of active vitamin D on their expression. Kidney protection and mechanism. Methods Uremic rats were induced by excising the right kidney and ligating the anterior branch of the left renal artery. The uremic rats were divided into uremia group (UC group) and uremia + 1,25 (OH) 2D3 group (UD group) . Normal rats as normal control group (NC group). At week 8, SBP, 24h urinary protein (UPC), serum calcium, phosphorus, 25 (OH) D3, fibroblast growth factor 23 (FGF23 )Level. The expressions of BMP-7 and TGF-β1 mRNA in glomeruli were detected by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of BMP-7 and TGF-β1 in glomeruli were detected by Western blotting. Results There was no significant difference in SBP between UC group and UD group, which were higher than NC group. Compared with the NC group, serum phosphorus, FGF23, 24 h UP, UPC significantly increased, and calcium, 25 (OH) D3 decreased in UC group. Compared with UC group, the levels of serum phosphorus, FGF23, 24 h UP, UPC and the serum calcium and 25 (OH) D3 were significantly increased in UD group. Compared with NC group, the expression of BMP-7 mRNA and protein in UC group was significantly down-regulated and the expression of TGF-β1 mRNA and protein were significantly up-regulated. Compared with UC group, the expression of BMP-7 mRNA and protein in UD group increased by 14.8% and 31.1%, while the mRNA and protein expression of TGF-β1 decreased by 35.7% and 43.9% respectively. Conclusions 1,25 (OH) 2D3 can not only improve the metabolism of calcium and phosphorus in uremic rats, but also increase the expression of BMP-7, decrease the expression of TGF-β1 and relieve the excretion of proteinuria and UPC.