摘要
目的：探讨一氧化碳释放分子2（CORM-2）在小鼠缺血再灌注损伤中发挥保护作用及其作用机制。方法：建立小鼠肾脏缺血再灌注损伤模型,给予CORM-2、重组高迁移率族蛋白1（rHMGB1）对小鼠肾脏缺血进行干预治疗,检测肾脏缺血再灌注后24h血肌酐、血尿素氮,评价肾脏功能情况。并对小鼠血浆中高迁移率族蛋白1（HMGB1）水平进行检测分析。结果：小鼠肾脏经历热缺血再灌注后出现明显肾功能损害（IRI组vs sham组,P〈0.05）,然而,给予CORM-2治疗能显著降低血浆肌酐和尿素氮升高水平,肾功能得到显著保护（CORM-2组vs IRI组、iCORM-2组,P〈0.05）。并且,在肾脏缺血再灌注过程中,CORM-2可以明显减少血浆HMGB1水平,显著抑制了HMGB1的核浆迁移释放,减轻缺血再灌注损伤,发挥保护肾脏功能作用。然而,输注外源性rHMGB1能显著逆转了CORM-2的保护作用（rHMGB1组vs CORM-2组,P〈0.05）。结论：在缺血再灌注损伤过程中,CORM-2通过抑制HMGB1核浆迁移释放下调炎症反应,从而减轻缺血再灌注损伤发挥保护效应。
Objective：To examine the relationship between the protective effect of carbon monoxide releasing molecule-2（CORM-2）and translocation of high mobility group box 1（HMGB1）in murine renal ischemia-reperfusion injury（IRI）.Methods：In the renal ischemia-reperfusion injury mice model,CORM-2,vehicle or recombinant HMGB1（rHMGB1）was administrated.The blood plasma was obtained at the end of 24 hours after reperfusion,CREA and UREA levels in the plasma were measured to estimate the degree of renal damage.Furthermore,the levels of HMGB1 in mouse plasma were detected at the end of 1 hour,12 hours and 24 hours of reperfusion after 50 minutes renal ischemia,ELISA was performed to evaluate the translocation of HMGB1.Results：We found that murine renal underwent 50 minutes warm ischemia resulted in severe renal damage.While,CORM-2 treatment markedly limited the increase of plasma CREAand UREA,ameliorated inflammation,then,protected against the renal IRI.Furthermore,CORM-2 pretreated significantly decreased the HMGB1 level in mice plasma,and inhibited HMGB1 nucleocytoplasmic shuttling and release.However,administration of the exogenous rHMGB1 could significantly eliminate the protective effect of CORM-2.Conclusion：In the process of ischemia reperfusion injury,CORM-2 may alleviate the inflammatory response by inhibiting renal epithelium HMGB1 nucleocytoplasmic shuttling and release,thereby attenuating the renal I/R injury in mice.
作者
阮永乐
王志维
周阎施婧
李博文
黄吉桢
RUAN Yongle;WANG Zhiwei;ZHOU Yanshijing;LI Bowen;HUANG Jizhen(Dept.of Cardiovascular Surgery,Renmin Hospital of Wuhan University,Wuhan 430060,China;Dept.of Plastic and Cosmetic Surgery,Hubei Maternal and Child Health Hospital,Wuhan 430070,China)
出处
《武汉大学学报（医学版）》
CAS
2018年第5期729-733,共5页
Medical Journal of Wuhan University
基金
国家自然科学基金青年项目(编号:81501376)
湖北省自然科学基金项目(编号:2015CFB345)
