p38MAPK通路参与肾间质纤维化的实验研究

Experimental study on the role of p38 mitogen-activated protein kinase pathway on the progression of renal interstitial fibrosis

目的:探讨p38丝裂素激活蛋白激酶(p38MAPK)在肾间质纤维化进展中的可能作用。方法:建立左侧输尿管梗阻模型(UUO组),设假手术组为对照组。于术后3d、7d和14d处死大鼠,应用比色法测定肾组织丙二醛(MDA)、超氧化物歧化酶(SOD)和羟脯氨酸(HYP)含量;免疫组化方法测定α-平滑肌肌动蛋白(α-SMA)和磷酸化p38MAPK(p-p38MAPK)的表达;Western blotting检测肾组织p38M APK和p-p38M APK的表达。结果:与对照组相比,UUO组3d、7d和14d大鼠肾组织MDA、HYP含量及α-SMA,p-p38MAPK的蛋白表达逐渐升高,SOD含量逐渐下降。结论:p38MAPK的活性在大鼠梗阻性肾病组织中明显增高,并伴有明显间质纤维化改变和氧化应激增强,提示p38MAPK的活化与氧化应激和肾间质纤维化有相关关系。

Objective.. To investigate the role of p38 mitogen-activated protein kinase（p38MAPK） in the progression of renal tubulointerstitial fibrosis. Methods： Eighteen wistar rats underwent UUO were killed at 3.7.14 days. Additional 7 rats Were sham operated as control. Renal fibrosis were assessed by the determination of tissue hydroxyproline （HYP）.malondialdehyde （MDA） and superoxide dismutase （SOD） content. Immunohistochemistry study was performed on renal tissue for α-smooth muscle actin （α-SMA） and phosphorylated p38MAPK （p- p38MAPK） . Western blotting of p38MAPK as well as p-p38MAPK were measured. Results..UUO induced a significant increase in MDA and HYP content, and a marked decrease in SOD. Conclusions：The activity of p38MAPK is increased significantly in the obstructed kidney with severe morphology changes and oxidative stress. P38MAPK activated by oxidative stress may play an important role in the renal tubulointerstitial fibrosis.