胞外调节蛋白激酶在糖尿病肾病系膜细胞中的信号传递作用

THE EFFECT OF EXTRACELLULAR REGULATED PROTEIN KINASE AS MESANGIAL CELL SIGALLING TRANSDUCERS IN DIABETIC NEPHROPATHY

目的 :研究胞外调节蛋白激酶 (ERK)在糖尿病大鼠肾脏中的表达及意义 ,并探讨其激活的机制。方法 :将大鼠肾脏系膜细胞进行体外培养 ,用激光共聚焦显微镜研究高糖、血管紧张素Ⅱ (AngⅡ )对系膜细胞ERK活性的影响。用链脲佐菌素 (STZ)复制糖尿病模型 ,于 2周时处死大鼠 ,取肾进行ERK免疫组化染色 ,检测其在肾脏中的表达。结果 :体外培养的正常细胞中 ,ERK定位于胞浆 ,当AngⅡ和高糖作用于系膜细胞后 ,可使ERK从胞浆转移至胞核。糖尿病大鼠肾小球ERK表达较正常大鼠明显增强 (P <0 .0 5 )。结论 :高糖和AngⅡ可激活系膜细胞ERK 。

Objective: To investigate the possible role of extracellular regulated protein kinase (ERK) of mesangial cells in the development of diabetic nephropathy.Methods: Rat mesangial cells were cuetured and laser confocal microscopy was used to study the expression and distribution of ERK in response to high glucose and angiotensin II. The expression of ERK in glomeruli of diabetic rats was detected by immunohistochemistry combined with computer-based image analysis method.Results:ERK was expressed in normal mesangial cells and located in cytosol.Hyperglycemia and angiotensin II resulted in the translocation of ERK from cytosol to the nucleus. The expression of ERK in glomeruli in diabetic rats was increased than that in normal rats(P<0.01). Conclusion:The increased expression of ERK by high glucose and angiotensin II constitutes an mechanism contributing to diabetic nephropathy.