活性维生素D3对糖尿病大鼠肾组织SHIP2表达及多态性的影响

目的：研究SHIP2基因多态性与糖尿病肾病（DN）的关系，观察应用活性维生素D-1，25-（OH）2D3]干预对SHIP2表达的影响。方法：选择健康雄性Wistar大鼠30只经腹腔注射链佐脲菌素（STZ）制备糖尿病模型，在糖尿病模型制备后给予1，25-（OH）2D3 0．03ng·g^-1·d^-1皮下泵入，连用8周。于模型成功后检测大鼠血糖（Glu）、24h尿蛋白（24hUP）、血肌酐（Scr）、尿足细胞（UPC）。采用RT—PCR检测肾小球SHIP2基因多态性的表达。结果：VitD3治疗后，SHIP2基因SNP5AA／ACGlu、24hUP较CC型明显下降，差异具有统计学意义（P〈0．05）。结论：SHIP2基因SNP5为AA／AC型者对VitD3的治疗反应优于GG型者。SHIP2基因SNP5多态性可能影响VitD3对T2DM患者的治疗效果。

Effect of active Vitamin D3 on the expression of SHIP2 gene single nucleotide polymor- phism in glomeruli of rats with diabetic nephropathy

Objective. To explore the relationship of nucleotide polymorphismobserve, and to ob- serve the effect of active vitamin D3 on the expression of SHIP2 gene single nucleotide polymorphism in glomeruli of rats with diabetic nephropathy（DN）. Methods： After 30 healhty Wistar rats diabetes models were successfully established by peritoneal injection of streptozotocin（STZ）, they were embedded with the osmotic minipump for giving 0. 03 ng ·g^-1 . d^-1 active vitamin D3 for 8 weeks. Blood glucose （Glu）, the ratio of 24-hoururinary protein（24 hUP）, serum creatinine（Scr） and urinary podoctye（UPC） were meas- ured. The expression and distribution of SHIP2 gene single nucleotide polymorphism in glomeruli was de- tected by indirect PCR-RFLP. Results. After Vit D3 treatmen, the levels of Glu （FPG） and 24hUP in the AG/AA genotype decreased significantly comparing with the AG/AA genotype （P〈0. 05）. Conclusion： T2DM rats with AG/AA genotype in the GG gene have a better therapeutic response to Vit D3 than pa- tients with AG/AA genotype.