一氧化碳释放分子CORM-2通过下调HMGB1迁移减轻肾脏缺血再灌注损伤

Carbon monoxide-releasing molecule CORM-2 protects against renal ischemia-reperfusion injury in mice by decrease HMGB1 nucleocytoplasmic shuttling

目的探讨一氧化碳释放分子CORM-2在小鼠缺血再灌注损伤中发挥保护作用与HMGB1迁移释放的关系.方法建立小鼠肾脏缺血再灌注损伤模型,检测肾脏缺血后组织中炎症因子HMGB1的变化及迁移释放,免疫组化及Western blot同时检测验证CORM-2治疗对肾IRI中HMGB1迁移释放的影响,探讨CORM-2发挥的保护作用及其效应的机制.结果在小鼠肾脏缺血损伤早期,肾脏肾小管上皮细胞大量HMGB1从胞核迁移至胞浆并释放至循环,从而启动的炎症反应,导致肾小管上皮细胞发生凋亡坏死.而缺血前1 h给予CORM-2治疗可以明显减少HMGB1的核浆迁移释放.病理及Western blot检测显示缺血损伤后,肾小管上皮细胞核中HMGB1明显释放,CORM-2治疗后肾小管上皮细胞核中HMGB1释放不明显(CORM-2组vs.IRI组,P<0.05).结论在缺血再灌注损伤早期,CORM-2可以显著减少肾小管上皮细胞中HMGB1核浆迁移释放,从而阻断炎症反应,减轻缺血再灌注损伤.

Objective To examine the relationship between the the protective effect of CORM-2 and translocation of HMGB1 in murine renal ischemia-reperfusion injury.Methods In the ischemia-reperfusion injury of mice,the translocation of HMGB1 after 50 minutes renal ischemia was evaluated.CORM-2 was administered 1 h before ischemia.Immunohistochemistry and Western blot were performed to examine the relationship between CORM-2 and HMGB1 nucleocytoplasmic shuttling in the murine renal ischemia-reperfusion injury.Results We found that HMGB1 released from the renal epithelium nucleus into cytoplasm significantly increased after renal ischemia.In contrast,CORM-2 pretreated significantly decreased the HMGB1 level in renal tubular epitheliums cytoplasm.Immunohistochemistry and Western blot were showed that amount of HMGB1 translocated from nucleus to cytoplasm in murine renal ischemia-reperfusion injury,whereas,pretreatment of CORM-2 significantly inhibited HMGB1 nucleocytoplasmic shuttling.Conclusions CORM-2 inhibits renal epithelium releasing HMGB1,an early mediator of inflammation,to attenuate the renal I/R injury in mice.