摘要
目的探讨P38MAPK与COX2在肾脏缺血预处理第二窗口的保护效应以及两者的信号转导关系,旨在阐明肾脏缺血预处理第二窗口保护的可能机制。方法雄性Wistar大鼠60只,随机分为5组,每组12只大鼠,分别为:假手术组(sham组),缺血再灌注组(IR组),缺血预处理+缺血再灌注组(IPC组),SB203580药物干预组(SB203580组),NS398药物干预组(NS398组),在再灌注后24h和48h两个时间点取材,用苦味酸法测定血清肌酐反映肾功能变化情况;用Western blot法检测肾组织P38MAPK与COX2蛋白的表达,进行半定量分析。结果血肌酐在IPC组较IR组低(P<0.05),尤其在IPC后48h明显(P<0.01);P38MAPK与COX2在sham组、IR组、IPC组均有表达,尤在IPC组表达明显(P<0.01);SB203580组无P38MAPK蛋白的表达,COX2的表达较IPC组低(P<0.05);在NS398组无COX2蛋白表达,P38MAPK蛋白表达与IPC组相比差异不明显(P>0.05)。结论P38MAPK作为COX2的上游物质参与了肾脏缺血预处理的第二窗口保护效应。
Objective To explore the relationship between P38 mitogen-activated protein kinase （P38 MAPK）and cyclooxygenase-2 （ COX2 ） in the rat kidney at the second window of protection of ischemic preconditioning （IPC） , and to clarify the possible mechanism of the second window protection in ischemic preconditioning. Methods Sixty male Wistar rats were randomly divided into 5 groups： sham group（ n = 12 ）, ischemic reperfusion group（ IR, n = 12 ） , ischemic preconditioning ＋ ischemic reperfusion group （ IPC, n = 12 ）, SB203580 （inhibitor of P38 MAPK ）group （n = 12 ） , NS398 （inhibitor of COX2 ）group （n = 12 ）. Rats were executed at hour 24 and 48 after reperfusion. The renal function was examined by measuring serum creatinine. The expression of P38 MAPK and COX2 protein in the renal tissue was assayed by Western blot. Results The level of serum creatinine was lower in IPC group than in IR group （P 〈 0.05 ） , and the lowest in IPC group at 48 h（ P 〈 0.01 ）. The P38 MAPK and COX2 protein were expressed in sham group, IR group and IPC group, especially higher in IPC group（ P 〈 0. 01 ）. No P38 MAPK expression was found in SB203580 group, while COX2 expression was lower than in IPC group（ P 〈 0.05 ）. In NS398 group, the protein expression of COX2 was not found, and the P38 MAPK expression was not significantly different from IPC group（ P 〉 0. 05 ）. Conclusion P38 MAPK and COX2 proteins are both involved in the second window protection of IPC, and P3s MAPK may be the upstream substance of COX2 protein.
出处
《山西医科大学学报》
CAS
2009年第12期1070-1073,共4页
Journal of Shanxi Medical University
基金
山西省朔州市科委基金资助项目
