中文摘要：

目的：探讨1,25二羟维生素 D3对糖尿病肾病（ DN）大鼠肾脏组织中转化生长因子β1（TGF-β1）、纤维连接蛋白（FN）、血管内皮生长因子（VEGF）表达的影响,阐明1,25二羟维生素D3对糖尿病大鼠肾脏是否具有保护作用以及可能机制。方法雄性SD大鼠注射链脲佐菌素建立DN模型,分为TGF-β1高表达组、TGF-β1高表达＋1,25二羟维生素D3组、TGF-β1低表达组、TGF-β1低表达＋1,25二羟维生素D3组、TGF-β1正常表达组、TGF-β1正常表达＋1,25双羟维生素D3组,1,25二羟维生素D3干预37 d后检测肾功能和血生化指标,观察大鼠肾脏组织形态学和纤维化程度,利用免疫组化、实时定量 PCR、Western印迹法检测大鼠肾脏TGF-β1、FN和VEGF的表达情况。结果与相应对照组相比,1,25二羟维生素D3干预组大鼠的总胆固醇、甘油三酯、血肌酐、血糖、HbA1C、24 h尿蛋白的水平均降低（P〈0.05）。 TGF-β1表达水平越高,肾脏纤维化程度越重,干预组大鼠的肾脏纤维化程度较对照组明显减轻。在各对照组中,不同组的TGF-β1 mRNA及蛋白表达差异有统计学意义（P〈0.05）,且伴随TGF-β1表达升高,FN、VEGF表达增加；干预组大鼠的TGF-β1、FN及VEGF较相应对照组表达均明显降低（P〈0.05）。结论1,25二羟维生素D3可能通过抑制肾脏TGF-β1、FN和VEGF的表达,对糖尿病大鼠的肾脏有保护作用。

英文摘要：

Objective To observe the effects of 1,25-dihydroxyvitamin D3 on the expressions of transforming growth factor-β1（TGF-β1）, fibronectin（FN）,and vascular endothelial growth factor（VEGF） in rats with diabetic nephropathy（DN）, and to elucidate the protective mechanism played by 1,25-dihydroxyvitamin D3. Methods DN models were estabolished by injecting streptozotoein （ STZ ） into male SD rats, which were divided into TGF-β1 overexpression group, TGF-β1 overexpression plus vitamin D3 group, TGF-β1 low-expression group, TGF-β1 low-expression plus vitamin D3 group, TGF-β1 normal-expression group, and TGF-β1 normal-expression plus vitamin D3 group. After 1,25-dihydroxyvitamin D3 treatment for 37 days, renal function and blood biochemical parameters were evaluated. The morphology and fibrosis of kidney tissues were observed. The expressions of TGF-β1, FN, and VEGF in kidney cortex were measured by immunohistochemistry, realtime PCR, and Western blotting. Results The levels of cholesterol, triglyceride, creatinine,plasma glucose, HbA1C , and 24 h urinary protein were lower in vitamin D3treated groups than those in corresponding control groups（P〈0. 05）. The degree of renal fibrosis was raised with the increased level of TGF-β1. Vitamin D3 treatment decreased the fibrosis in diabetic kidney. There were significant differences in the mRNA and protein expressions of TGF-β1 in three control groups（P〈0. 05）. With the increased levels of TGF-β1, the expressions of FN and VEGF were increased. The expressions of TGF-β1, FN, and VEGF were lowered by vitamin D3compared with the corresponding control groups（P〈0. 05）. Conclusion 1,25-dihydroxy-vitamin D3 may protect the renal tissure in diabetic rats via inhibiting the expressions of TGF-β1, FN, and VEGF in the kidney.