瘦素预处理和缺血预处理在小鼠心肌缺血／再灌注损伤中的心肌保护机制  

Amelioration of myocardial ischemia/reperfusion injury by leptin pretreatment and ischemic preconditioning in mouse

作　　者：徐彤彤[1] 刘世平[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：《中国危重病急救医学》2010年第2期105-108,共4页Chinese Critical Care Medicine

基　　金：广西科技开发计划项目（0993003C-18）;广西教育厅科研项目（200810LX464）;广西桂林市科技开发项目（20080211）

摘　　要：目的观察瘦素预处理和缺血预处理（IPC）对心肌缺血／再灌注损伤（MIRI）模型小鼠的心肌保护作用，探讨瘦素参与的机制。方法将36只C57BL／6小鼠按随机数字表法分为5组：①假手术组（12只）；②短暂缺血／再灌注（I／R）组（6只）：缺血3min后再灌注5min，进行3个短暂的循环；③标准I／R组（6只）：缺血30min后再灌注120min；④1PC组（6只）：行3个短暂I／R循环后再进行标准I／R操作；⑤瘦素预处理组（6只）：缺血前30min腹腔注射50μg／kg小鼠重组瘦素。假手术组和短暂I／R组分别于再灌注后0（即刻）、5、30、120min取血，动态监测血清瘦素水平；其余各组于再灌注后120min处死小鼠，观察心肌梗死面积、心肌瘦素水平、髓过氧化物酶（MP0）活性，以及血清瘦素、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平。结果短暂I／R处理后5rain血清瘦素水平即较假手术组同期显著升高[（6．24±2．34）μg／L比（1．35±0．45）μg／L]，30min达峰值[（12．36±1．33）μg／L]，之后逐渐下降，与假手术组水平同期比较差异无统计学意义[（1．96±1．33）μg／L比（1．16±0．25）μg／L，P〉0．053。与标准I／R组比较，瘦素预处理组与IPC组均可显著缩小梗死面积[（11．50±2．26）％、（9．00±1．90）％比（37．00±2．53）％]，降低心肌瘦素[（8．36±3．42）μg／g、（6．71±2．03）μg／g比（15．51±3．92）μg／g]、MPO[（17．10±3．95）μg／g、（13．33±2．88）μg／g比（30．83±4．06）μg／g3以及血清瘦素[（15．03±1．87）μg／L、（11．85±0．72）μg／L比（29．55±2．31）μg／L3、TNF-α[（35．10±10．12）ng／L、（27．04±5．18）ng／L比（81．34±14．20）ng／L3、IL-6[（167．39±72．83）ng／L、（149．13±37．69）ng／L比（477．30±29．09）ng／L3水平（均P〈0．01）。结论低剂量瘦素预处理可模仿经典Objective To study the effects and role of leptin pretreatment and ischemic preconditioning （IPC） on the reduction of myocardial ischemia/reperfusion injury （MIRI） in mouse. Methods Thirty-six male C57BL/6 mice were randomized into five groups： （1）sham operation group （n= 12） 3 （2） brief ischemia/reperfusion （I/R） treatment group （n= 6）, in which the mice were subjected to three cycles of a 3-minute regional ischemia followed by a 5-minute reperfusion （I/R cycle） ; （3） MIRI group （n= 6）, in which MIRI was established in the mice by blocking anterior descending branch of left coronary artery for 30 minutes, followed by 120 minutes reperfusion; （4） IPC group （n= 6）, in which three I/R cycles were performed on the mice followed by the MIRI protocol; （5） leptin pretreatment group （leptin group, n= 6）, in which 50 μg/kg of leptin was injected intraperitoneally to the mice 30 minutes before myocardial ischemia. From 6 mice of the sham operation group and from the mice of brief I/R group, serum samples were collected at different time points （0, 5, 30 and 120 minutes） after reperfusion to measure changes in serum leptin level. From the rest of the mice, blood and heart samples were harvested at 120 minutes after reperfusion to analyze the myocardial function and infarct size, leptin, myeloperoxidase （MPO）, tumor necrosis factor-α （TNF-α）, and interleukin-6 （IL-6） levels. Results IPC procedure resulted in an increase in serum leptin level shortly after reperfusion. The leptin level increased significantly than that of sham operation group （（6.24±2.34） μg/L vs. （1.35±0.45） μg/L] at 5 minutes after I/R, and reached the peak value of （ 12.36± 1.33） μg/L at 30 minutes after I/R. Then it gradually decreased to its original （0 minute after reperfusion） value [（1.96±1.33） μg/L3 at 120 minutes after I/R. There was no difference compared with sham operation group （（1.16 ± 0. 25） μg/L, P〈0.05]. Administration of lep

关 键 词：缺血预处理 瘦素预处理 缺血/再灌注损伤 心 炎症细胞因子 

分 类 号：R541[医药卫生—心血管疾病] R512.6[医药卫生—内科学]