活性维生素D3对肾小球上皮间质转化的影响研究

目的:观察活性维生素D₃（1,25-（OH）₂D₃）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）₂D₃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）₂D₃治疗组（DD）,后者给与1,25-（OH）₂D₃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）₂D₃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。

Effect of 1,25-dihydroxyvitamin D3 on Glomerular Epithelial-mesenchymal Transition

Objective： To observe the effects of 1,25-dihydroxyvitamin D3 1,25-（OH） 2D3 ] on the expressions of podocyte marker Nephrin, mesenchymal transition marker Snail and mesenchymal marker Desmin in the glomeruli of diabetic rats, and investigate the role of 1,25 （OH） 2 D3 in epithelial-mesenchymal transition （EMT）. Method： 24 diabetic rats induced by streptozotocin （STZ） were randomly divided into untreated group and 1,25 （OH）2 D3 treated group （DD） with the dose of 3 ng·100 g^-1 body weight·day^-1 by a subcutaneous osmotic minipump. Another 10 normal rats served as the control group （NC）. After blood glucose （BG） ,24 h urinary protein （24 h UP） and urinary podocytes （UPC） were measured in the 6th week,the rats were sacrificed to determine glomcrular Nephrin, Snail, Desmin mRNA and protein expressions by RT-PCR and Western blot, respectively. Result： Untreated group showed significantly increased BG,24 b UP, the mRNA and protein expressions of Snail and Desmin with decreased Nephrin, and no difference in UPC when compared with those in NC group. There was no significant difference in BG and UPC between DD and untreated group. 24 h UP was significantly lower in DD group than that in untreated group. Glomerular Nephrin mRNA and protein expression were increased, and Snail and Desmin were decreased in the DD group when compared with those of the untreated group. Conclusion： 1,25 （OH）2 D3 can up-regulate the expressions of glomerular Nephrin, down-regnlate the expressions of Snail and Desmin, and inhibit EMT to alleviate renal injury.