瘦素预处理对小鼠心肌冷缺血-再灌注损伤的保护作用研究  

Preteatment of leptin exhibits direct cardioprotective effects on cold myocardial ischemia reperfusion injury in mice

作　　者：徐彤彤[1] 王一锦[1] 王晓珊[1] 

机构地区：[1]桂林医学院附属医院特需病区,广西541001

出　　处：《中国急救医学》2010年第8期711-715,I0001,共6页Chinese Journal of Critical Care Medicine

基　　金：2010年广西自治区卫生厅重点课题（No.重2010050）;2009年广西科学研究与技术开发计划课题（桂科攻0993003C-18）;2008年广西教育厅项目（No.200810LX464）

摘　　要：目的本实验旨在研究同种小鼠腹部心脏移植模型中，瘦素预处理对心肌缺血-再灌注损伤的保护作用及其可能机制。方法雄性C57BL／6小鼠行同种间小鼠腹部心脏移植，供体置于4℃UW液中保存6h。受体随机分为两组：瘦素预处理（Leptin）组，12只，小鼠重组瘦素50μg／kg溶人生理盐水（normalsaline，NS）200μL中，于心脏移植前腹腔保留；NS对照组，12只，心脏移植前NS200灿于腹腔保留。另设假手术组，12只。分别于术后6、24h收获移植心脏与血清标本（每个时间点每组6个标本），评价移植心脏功能及组织形态学变化，检测小鼠移植心脏及血清瘦素的水平，同时测定中性粒细胞活性、炎性细胞因子水平等，并比较两组移植心脏的3周存活时间（每组n=10）。结果与对照组比较，瘦素预处理显著降低移植小鼠血清心肌肌钙蛋白I，改善移植心脏功能评分；瘦素预处理显著降低心脏移植小鼠术后供心心肌及血清瘦素水平；降低心肌MPO活性，减少血清细胞炎性因子TNF-α、IL-1B、IL-6的水平；瘦素预处理组60％的移植心脏在术后3周仍然搏动有力，而对照组所有供心在2周内停止跳动。结论瘦素预处理显著减轻心肌冷缺血-再灌注损伤，改善心肌功能，提高移植心脏存活时间，其保护作用可能与减轻炎症反应有关。Objective To explore the role of the leptin on cold myocardial ischemia reperfusion injury in a murine cardiac transplant model. Methods Syngeneie heart transplants were performed in male C57BL/6 mice. Donor hearts were subjected to 6 h of cold ischemia and receipts were randomized into 2 groups, including normal saline control group （n = 12 ） and the leptin pretreatment group （n = 12 ）. And the sham -operation group（ n = 12 ）. Leptin 50μg/kg in 200μL NS injected intraperitoneally before transplantation （ at about 30 min before reperfusion） in leptin - pretread group. The grafts were retrieved at 6 and 24 h after reperfusion （ n = 6 at each time point）. Grafts and serum samples were collected for leptin measurement, eytokines analysis and histological analysis to assess intra - graft inflammation. The survival of cardiac grafts was compared between the 2 experimental groups over a three - week period （ n = 10 each group）. Results The scores of cardiac grafts function and histology in leptin group was significantly higher than these in NS groups. Administration of leptin before reperfusion significantly reduced the myocardial and serum leptin level. Furthermore, leptin pretreatment significantly reduced serum umor necrosis factor - alpha, interleukin - 1β and interleukin - 6 levels and myocardial myeloperoxidase level. Leptin -treated organs exhibited improved histology and signifieantly reduced neutrophil and lymphocyte infiltration compared with NS - treated organs. Finally, 60% the leptin - treated heart grafts retained strong beating up to the end of the observation period （ 3 weeks ）, whereas all control grafts lost function within 2 weeks. Conclusion Pretreatment of leptin is a feasible and effective method of attenuating ischemia/reperfusion injury, protecting cardiac function, and prolonging graft survival. This cardioprotection is mediated, in part, via suppression of inflammation.

关 键 词：瘦素 缺血-再灌注损伤 心脏移植 炎症 

分 类 号：R542.2[医药卫生—心血管疾病]