12-脂氧化酶基因敲除对1型糖尿病肾病小鼠肾小球内纤维连接蛋白表达的影响

Effect of 12-lipoxygenase gene knockout on the fibronectin expression in type 1 diabetic nephropathy mouse glomeruli

目的探讨12-脂氧化酶(12-lipoxygenase,12-LO)对1型糖尿病肾病小鼠肾小球内纤维连接蛋白(Fibronectin,FN)表达的影响。方法用链脲佐菌素(Streptozotocin,STZ)诱导1型糖尿病模型。野生型和12-LO基因敲除C57BL/6小鼠随机分成4组:野生型对照组;12-LO基因敲除组;野生型糖尿病组;12-LO基因敲除糖尿病组。采用RT-PCR和免疫组化方法分别检测肾小球内FN mRNA和蛋白表达的变化。结果与野生型对照组比较,野生型1型糖尿病小鼠血糖(P<0.01)、肾重/体重比值(P<0.01)和24小时尿白蛋白明显增高(P<0.01),但12-LO基因敲除糖尿病小鼠尿白蛋白(P<0.05)、肾重/体重比值(P<0.05)明显低于野生型糖尿病小鼠。基础情况下,野生型和12-LO基因敲除小鼠肾小球内FN表达无差异。与野生型对照组相比,野生型糖尿病小鼠肾小球内FN表达明显增加(P<0.01),但12-LO基因敲除可阻止糖尿病小鼠肾小球FN表达的增加(P<0.05)。结论 12-LO基因敲除延缓1型糖尿病肾病小鼠蛋白尿的进展,降低肾小球内FN表达。

Objective To investigate the effect of 12-lipoxygenase（12-LO） knockout on the fibronectin（FN） expression in type 1 diabetic nephropathy mouse glomeruli.Methods In type 1 model of DN,C57BL/6 mice were made diabetic using streptozotocin（STZ） injections.The C57BL/6 mice were divided into four groups：wild type control group（WT）,12-LO knockout mice group（LOKO）,wild type diabetic mice group（WT＋STZ）,12-LO knockout diabetic mice group（LOKO＋STZ）.The levels of FN were determined using RT-PCR and immunohistochemistry respectively.Results Blood glucose,kidney/body weight ratio and 24 hour urinary protein were increased in WT＋STZ group compared with WT control group（P0.01）.However,urine protein,Kidney/body weight ratio were decreased in LOKO＋STZ group compared with WT＋STZ group（P0.05）.FN expression were increased in WT＋STZ group compared with WT control group（P0.01）.However,FN expression were decreased in LOKO＋STZ group compared with WT＋STZ group（P0.05）.Conclusion 12-LO knockout can ameliorate the progression of proteinuria and glomeruli FN upregulation in type 1 diabetic nephropathy mouse.