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目的:观察活性维生素D_3(1,25-(OH)_2D_3)对糖尿病大鼠肾小球足细胞标志蛋白Nephrin,间质转化标志蛋白Snail及间质标志蛋白Desmin表达的影响,探讨1,25-(OH)_2D_3在上皮间质转化中的作用。方法:24只链脲菌素诱导的糖尿病大鼠随机分为糖尿病组(DM)和1,25-(OH)_2D_3治疗组(DD),后者给与1,25-(OH)_2D_3按3 ng·100 g~(-1)·d~(-1)皮下注射。另以10只大鼠作为对照组(NC)。于6周检测血糖(BG)、24 h尿蛋白(24 h UP)、尿液足细胞(UPC)。处死大鼠,PT-PCR及Westernbolt分别测定肾小球Nephrin、Snail、Desmin mRNA和蛋白质的表达。结果:DM组BG、24 h UP较NC组显著升高,而UPC与NC组相比无显著差异。DM组肾小球Nephrin mRNA和蛋白质的表达水平较NC组显著降低,而Snail、Desmin mRNA和蛋白表达显著增加。DD组BG、UPC与DM组相比无显著差异,而24 h UP较DM组显著降低,肾小球Nephrin mRNA和蛋白质的表达较DM组升高,而Snail、Desmin mRNA和蛋白表达降低。结论:1,25(OH)_2D_3上调Nephrin的表达,并减少Snail、Desmin的表达,可抑制上皮间质转化,减轻肾损伤。
Objective: To investigate the effects of active vitamin D_3 (1,25- (OH) _2D_3) on glomerular podocyte markers Nephrin, interstitial transforming protein Snail and interstitial protein Desmin in diabetic rats, (OH) _2D_3 in epithelial mesenchymal transition. Methods: Twenty-four streptozotocin-induced diabetic rats were randomly divided into diabetic group (DM) and 1,25- (OH) _2D_3 treatment group (DD), and the latter given 1,25- (OH) ng · 100 g ~ (-1) · d ~ (-1) subcutaneously. Another 10 rats served as the control group (NC). Blood glucose (BG), 24 h urine protein (24 h UP), urinary podocyte (UPC) were measured at 6 weeks. The rats were sacrificed, and the expressions of Nephrin, Snail, Desmin mRNA and protein in glomerulus were detected by PT-PCR and Westernbolt respectively. Results: The levels of BG and 24 h UP in DM group were significantly higher than those in NC group, but there was no significant difference between UPC group and NC group. Nephrin mRNA and protein expression of glomeruli in DM group were significantly lower than those in NC group, but Snail, Desmin mRNA and protein expression were significantly increased. Compared with DM group, the expression of Nephrin mRNA and protein in glomerulus increased, whereas the expression of Snail, Desmin mRNA and protein decreased in 24 h UP group compared with DM group. CONCLUSION: 1,25 (OH) _2D_3 can up-regulate the expression of Nephrin and decrease the expression of Snail and Desmin, which can inhibit epithelial-mesenchymal transition and reduce renal injury.