蛋白激酶受体2在糖尿病大鼠肾组织中的表达及意义

目的通过观察蛋白激酶受体2（PAR-2）在糖尿病（DM）大鼠肾组织中的表达情况,探讨其在糖尿病肾病肾小管间质纤维化中的可能作用。方法将60只雄性Sprague-Dawley大鼠随机分为对照组（C组）、糖尿病组（DM组）和用药组（T组）,DM组和T组大鼠腹腔注射链脲佐菌素55 mg/kg制备DM模型,分别于实验的第2、4、8、12、20周处死大鼠后取肾组织制片,在电镜下观察肾组织形态改变;采用免疫组化检测四型胶原（ColⅣ）蛋白和PAR-2在肾组织中表达情况,并采用病理图像分析软件进行半定量分析。结果 C组大鼠肾组织ColⅣ表达均微弱;DM组大鼠肾组织ColⅣ表达逐渐增强,与C组比较差异有统计学意义;T组大鼠肾组织ColⅣ表达增强后又逐渐减弱,与DM组比较差异有统计学意义。C组大鼠肾组织无PAR-2表达或仅微量表达于血管内皮;DM组大鼠在实验的第2周开始出现PAR-2表达,并随实验进程PAR-2表达逐渐增强,与C组比较差异有统计学意义;T组大鼠肾组织PAR-2的表达与DM组比较差异无统计学意义。结论 PAR-2早期表达于糖尿病肾病大鼠的近曲小管上皮细胞,肾组织中PAR-2表达的变化趋势提示PAR-2可能参与了糖尿病肾病的肾间质纤维化过程。

Expression and implication of protease activated receptor-2 in kidney of diabetic nephropathy rats

Objective To observe the expression of protease activated receptor-2 in kidney of diabetic nephropathy rats and to investigate its contribution to the progression of diabetic in tubulointerstitial fibrosis of diabetic nephropathy rats. Methods Streptozotocin-induced diabetic rats were sacrificed at 2w,4w,8d,12w and 20w respectively. The renal pathological changes were examined with protein expression of collagen Ⅳ （Col Ⅳ）. The protein expression of PAR-2 and collagen Ⅳ in kidney were detected by immunohistochemistry, the mRNA expression of PAR-2 was detected by reverse transcription polymerase chain reaction. Using an image analyzer with microscopy to analyse the correlation. Results Total PAR-2 mRNA levels started to rise in diabetic kidneys at 2W, reaching its peak at 8W, and reduced slightly at 12w and 20w. PAR-2 mainly expressed in renal tubular epithelial cells, especially in proximal tubular cells. It also located in renal capillary ansa,interstitial infiltrate cells and fibroblast. Conclusion PAR-2 mainly expressed in the renal proximal convoluted tubule epithelial cells in early diabetic rats,expression of PAR-2 in the diabetic rats shows that PAR-2 may play a role in tubulointerstitial fibrosis of diabetic nephropathy.