CAJ | 학술논문

目的探讨一氧化碳释放分子2 (CORM-2)对小鼠肾脏缺血再灌注损伤的作用及其效应.方法制备Balb/c小鼠原位肾脏缺血再灌注模型:在32℃下完全阻断小鼠左肾血流40 min,然后恢复血流灌注,同时切除小鼠对侧肾脏.小鼠分别于术前1h经尾静脉注射CORM-2溶液(CORM-2组)或失活CORM-2溶液(iCORM-2组),另设假手术组作为对照.再灌注24 h后,检测各组小鼠肾功能,取肾脏组织行HE和原位末端转移酶标记染色检查,评价其肾脏组织损伤程度.再灌注1、3、7d后,取小鼠肾脏组织进行免疫组织化学和免疫荧光检测,观察小鼠肾缺血再灌注损伤过程中炎症反应的情况.结果 IRI组出现明显肾功能损害,其小鼠血肌酐和尿素氮水平与假手术组相比较,差异均有统计学意义(P＜0.05);CORM-2组肾功能损害程度减轻,其小鼠血肌酐和尿素氮水平低于IRI组和iCORM-2组(P＜0.05).常规病理学检查发现,IRI小鼠肾脏组织中肾小管上皮细胞发生凋亡坏死;CORM-2组肾小管上皮细胞的凋亡减轻.IRI组小鼠缺血再灌注损伤早期(再灌注1d和3 d),肾脏组织中出现大量MPO阳性中心粒细胞和肿瘤坏死因子α,介导急性炎症反应.CORM-2组MPO阳性中性粒细胞浸润和肿瘤坏死因子α产生明显减少.结论 CORM-2可以减轻小鼠肾缺血再灌注中的炎症反应,发挥保护作用.
목적 탐토일양화탄석방분자2 (CORM-2)대소서신장결혈재관주손상적작용급기효응.방법 제비Balb/c소서원위신장결혈재관주모형:재32℃하완전조단소서좌신혈류40 min,연후회복혈류관주,동시절제소서대측신장.소서분별우술전1h경미정맥주사CORM-2용액(CORM-2조)혹실활CORM-2용액(iCORM-2조),령설가수술조작위대조.재관주24 h후,검측각조소서신공능,취신장조직행HE화원위말단전이매표기염색검사,평개기신장조직손상정도.재관주1、3、7d후,취소서신장조직진행면역조직화학화면역형광검측,관찰소서신결혈재관주손상과정중염증반응적정황.결과 IRI조출현명현신공능손해,기소서혈기항화뇨소담수평여가수술조상비교,차이균유통계학의의(P＜0.05);CORM-2조신공능손해정도감경,기소서혈기항화뇨소담수평저우IRI조화iCORM-2조(P＜0.05).상규병이학검사발현,IRI소서신장조직중신소관상피세포발생조망배사;CORM-2조신소관상피세포적조망감경.IRI조소서결혈재관주손상조기(재관주1d화3 d),신장조직중출현대량MPO양성중심립세포화종류배사인자α,개도급성염증반응.CORM-2조MPO양성중성립세포침윤화종류배사인자α산생명현감소.결론 CORM-2가이감경소서신결혈재관주중적염증반응,발휘보호작용.
Objective To investigate if the administration of CORM-2 can provide protection against renal ischemia-reperfusion injury (IRI).Method Murine renal ischemia was induced by clamping left renal pedicles for 40 min with vascular micro damps at 32 C,then the contralateral kidney was removed.CORM-2 or vehicle was administered via intravenous infusion 1 h before the onset of ischemia.The blood plasma and renal samples were obtained at 24 h after reperfusion to assess renal function and cellular injury.Plasma Cr and BUN levels,HE and TUNEL were performed to estimate the magnitude of renal damage.Kidneys were retrieved from indicated animals at various time points after renal IRI,and the sections were prepared for histological evaluation.MPO staining procedures were performed to assess the neutrophils infiltration in the renal IRI.Besides,Immunofluorescent stain of TNF-α was performed on the kidneys which were retrieved from indicated animals to determine the production of inflammatory mediators in renal I/R.Results The plasma Cr and BUN were significantly increased at 24 h after reperfusion in IRI control mice,and CORM-2 treatment could markedly diminish the increase of plasma Cr and BUN in mice subjected to I/R.In parallel,histological analysis demonstrated that CORM2 treatment markedly reduced apoptosis of the renal tubular epithelium cells and hemorrhage.IRI caused marked infiltration and accumulation of the MPO-positive neutrophils in renal interstitium.Administration of CORM-2 before ischemia dramatically inhibited neutrophils infiltration as compared with IRI or iCORM-2 group.Furthermore,we confirmed that CORM-2 markedly decreased production of TNF-α.Conclusion Carbon monoxidereleasing molecule CORM-2 could ameliorate inflammation to protect against the renal IRI in mice.