糖尿病大鼠肺组织p38 MAPK活性变化的研究

目的:观测糖尿病大鼠肺组织的病理改变及p38MAPK活性的变化。方法:复制糖尿病(DM)大鼠模型,4周后观察其肺部组织病理改变;采用改良的Takay法测定蛋白激酶C(PKC)活性,蛋白质免疫印迹分析(Westernblot)及免疫组化方法检测转化生长因子β₁在DM大鼠肺组织表达变化并以原位杂交方法检测丝裂原激活的蛋白激酶p38(p38MAPK)活性。结果:DM大鼠4周后毛细血管壁及肺泡间隔增厚,肺间质胶原成份增多,TGF-β₁在肺组织表达增多,肺组织PKC、p38MAPK活性增强。结论:链脲菌素糖尿病大鼠肺组织高糖环境下细胞内外信号传导系统PKC-p38MAPK被激活,可能参与糖尿病肺部并发症的发生和发展。

Alteration of p38 MAPK activity in lung tissue in diabetic rats

AIM: To observe the pathologic changes in lung and the role of p38 MAPKinase signal pathways in pulmonary alteration in diabetic rats. METHODS: Diabetic rats were induced by intraperitoneally injected streptozotozin (STZ). After 4 weeks, we observed the pathologic changes in lungs, tested protein kinase C (PKC) activities by isotope in lungs of model rats, tested transforming growth factor (TGF-β₁) by Western blotting and immunohistochemical analysis, and determined the expression of p38 MAPKinase mRNA using in situ hybridization.RESULTS: After STZ administration for 4 weeks, we observed thickened pulmonary capillary basal lamina and increased number of fibre in Diabetes mellitus (DM) rats. TGF-β₁ levels, PKC and p38 MAPK activities were also found increased. CONCLUSION: The increased activities of TGF-β₁ and p38 MAPK suggeste that TGF-β₁ may play an important role in diabetic lung, and hyperglycemia-PKC-p38 MAPK signal pathways may be involved in the pathogenesis of diabetes.