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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。
Objective To investigate the possible role of PAR-2 in the development of renal tubulointerstitial fibrosis in diabetic nephropathy by observing the expression of protein kinase 2 receptor (PAR-2) in the kidney of diabetic rats. Methods Sixty male Sprague-Dawley rats were randomly divided into control group (C group), diabetic group (DM group) and medication group (T group). Rats in DM group and T group were intraperitoneally injected with streptozotocin (55 mg) / kg DM model were made, the rats were sacrificed on the 2nd, 4th, 8th, 12th and 20th week respectively after the rats were sacrificed and the kidneys were sacrificed. The morphological changes of the kidney were observed under electron microscope. The expressions of collagen type Ⅳ ) Protein and PAR-2 expression in renal tissue, and semi-quantitative analysis using pathological image analysis software. Results The expression of ColⅣ in renal tissue of rats in C group was weak. The expression of Col Ⅳ in renal tissue of diabetic rats increased gradually, which was significantly different from that in C group. The expression of Col Ⅳ in renal tissue of T group increased gradually and then decreased, The difference was statistically significant. No expression of PAR-2 or only a small amount of expression in the vascular endothelium was found in the kidney of group C; PAR-2 expression began to appear in the DM group at the second week of the experiment, and gradually increased with the progress of the experimental course, The difference was statistically significant; T group rats kidney tissue PAR-2 expression compared with the DM group, no significant difference. CONCLUSIONS: The expression of PAR-2 is closely related to the expression of PAR-2 in proximal tubule epithelial cells of diabetic nephropathy rats. PAR-2 may be involved in the process of renal interstitial fibrosis in diabetic nephropathy.