丝裂素活化蛋白激酶亚类在急性缺血/再灌注肾损伤修复过程中的变化  

Changes of subfamilies of mitogen-activated protein kinases in recovery process of acute renal ischemia/reperfusion injury

作　　者：蔡琪[1] 李晓玫[1] 王海燕[1] 

机构地区：[1]北京医科大学第一医院肾内科暨肾脏病研究所,北京100034

出　　处：《中国病理生理杂志》2000年第6期527-528,共2页Chinese Journal of Pathophysiology

基　　金：教育部博士点基金 (95 0 10 2 9);跨世纪优秀人才基金资助项目 (39910 2 10 474- 2 31-C0 4)

摘　　要：目的 :研究急性缺血 /再灌注肾损伤修复时丝裂素活化蛋白激酶 (MAPKs)亚类细胞外信号调节激酶 (ERK)、c -Jun氨基末端激酶 (JNK)的变化 ,探讨其在肾损伤修复中的意义。方法 :夹闭大鼠双侧肾蒂造成急性缺血 /再灌注肾损伤模型 ,应用电镜观察肾组织形态学改变 ,免疫组化法检测肾组织增殖细胞核抗原 (PCNA)表达 ,采用特异性底物磷酸化结合免疫沉淀法测定肾组织的ERK、JNK活性。结果 :急性缺血后再灌注 2h肾小管上皮细胞腔面微绒毛重新出现 ,肾小管PCNA阳性细胞开始增加 ;缺血 45min使ERK活性降低 ,再灌注 5minERK活性完全恢复 ;缺血 45min对JNK活性无影响 ,再灌注 5minJNK活性增加并持续到再灌注 2h。结论 :MAPKs活性变化 ,特别是JNK活性增加参与了急性缺血 /再灌注肾损伤早期细胞修复过程。AIM: To investigate the change and the possible role of mitogen-activated protein kinase(MAPK) subfamilies in early recovery process following acute renal ischemia/reperfusion injury. METHODS: Ischemia/reperfusion renal injury model was made by placing an atraumatic vascular clamp in renal pedicel. The morphologic change was observed by transmission electron microscope. The proliferating cell nuclear antigen(PCNA) positive renal cells were detected by immunohistochemistry. Extracellular signal-regulated kinase (ERK) and c-Jun NH 2-terminal kinase(JNK) activity was assayed by specific substrate phosphorylation with immunoprecipitation. RESULTS: After acute ischemia, microvilli in renal tubular cells appeared again after 2h of reperfusion. At the same time, the PCNA-positive cells were initially increased. ERK activity decreased at 45 min of ischemia, and completely recovered at 5 min of reperfusion. JNK activity was not influenced by ischemia, but increased at 5 min of reperfusion, reaching its maximal activity at 20 min of reperfusion, and prolonged within 2h reperfusion. CONCLUSION: After renal ischemia/reperfusion injury, the early recovery of renal tubule damage was related to the changes of MAPKs in which the increase of JNK activity might be more important.

关 键 词：再灌注损伤 缺血 肾损伤 丝裂素活化蛋白激酶 

分 类 号：R692.02[医药卫生—泌尿科学]