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目的动态观察糖尿病(DM)大鼠肾小管骨形态发生蛋白-7(BMP-7)和p38丝裂原活化蛋白激酶(p38MAPK)在糖尿病肾病(DN)发病机制中的相互关系。方法将SD大鼠分为正常对照组(N组)、糖尿病组(DM组)和糖尿病胰岛素治疗组(DMT组),分别于成模后2、4、8、12、16和24周测定生化指标和肾脏指数,PAS染色观察肾脏病理形态改变,免疫组织化学检测BMP-7、p-p38MAPK、α-SMA和FN蛋白的表达;RT-PCR方法检测肾皮质BMP-7mRNA的表达。结果随DM病程延长,BMP-7蛋白和mRNA的表达较N组低,至24周时BMP-7蛋白仍有少量表达但mRNA无表达,DMT组表达显著增多;p-p38MAPK蛋白于N组无表达,DM组显著增多,8周时达高峰,DMT组则显著减少;α-SMA开始表达于DM16周组,而DMT组无表达。24周DM组和DMT组BMP-7蛋白表达与24h尿蛋白、肾脏指数、α-SMA、FN和p-p38MAPK呈显著负相关。结论BMP-7与p38MAPK之间可能相互调节,共同参与糖尿病肾病的发生发展过程。
Objective To investigate the relationship between BMP-7 and p38 mitogen activated protein kinase (p38MAPK) in the pathogenesis of diabetic nephropathy (DN) in diabetic rats. Methods SD rats were divided into normal control group (N group), diabetes mellitus group (DM group) and diabetic insulin treatment group (DMT group). The rats were sacrificed at 2, 4, 8, 12, The expression of BMP-7, p-p38MAPK, α-SMA and FN protein were detected by immunohistochemical staining and the expression of BMP-7 mRNA in renal cortex by RT-PCR. Results The expression of BMP-7 protein and mRNA was lower with the prolongation of DM. Compared with N group, the expression of BMP-7 protein was still low at 24 weeks but not in DMT group. The expression of p-p38MAPK protein in N group DM group increased significantly, peaked at 8 weeks and decreased significantly in DMT group. Α-SMA began to express in DM16 weeks group, but not in DMT group. BMP-7 protein expression in 24-week DM group and DMT group was negatively correlated with 24h urinary protein, renal index, α-SMA, FN and p-p38MAPK. Conclusion BMP-7 and p38MAPK may regulate each other and participate in the development of diabetic nephropathy.