酒石酸布托啡诺预处理对小鼠心肌缺血再灌注损伤的保护作用及其机制-东南大学学报医学版

酒石酸布托啡诺预处理对小鼠心肌缺血再灌注损伤的保护作用及其机制

单位：1. 南京医科大学第一附属医院胸心外科, 江苏南京 210029;
2. 盐城市第一人民医院重症医学科, 江苏盐城 224000

分类号：R452

出版年·卷·期（页码）：2017·36·第一期（74-77）

摘要：

目的：探讨酒石酸布托啡诺预处理对小鼠心肌缺血再灌注损伤的保护作用及其机制。方法：取雄性C57BL/6小鼠30只，随机分为3组，每组10只。缺血再灌注组（I/R组）结扎左冠状动脉前降支（LAD）30 min，再灌注6h；布托啡诺预处理组（B+I/R组）在缺血前30min经后肢肌肉注射酒石酸布托啡诺40μg·kg^-1，余处理同I/R组；假手术组（Sham组）开胸暴露心脏，仅LAD穿线但不结扎。Sham组和I/R组小鼠在缺血前30min肌肉注射等体积生理盐水。再灌注6h后，采集腹主动脉血样，酶联免疫吸附法测定血清肿瘤坏死因子α（TNF-α）、肌酸激酶同工酶（CK-MB）和肌钙蛋白Ⅰ（CTnⅠ）的浓度；Western blot法测定心肌组织Cleaved caspase 8、Cleaved caspase 3、p-JNK和JNK的表达；凝胶电泳迁移率（EMSA）法测定心肌组织核因子-κB（NF-κB）结合活性。结果：与Sham组比较，I/R组血清CK-MB、CTnI和TNF-α水平显著升高（均P<0.05），心肌组织Cleaved caspase 8和Cleaved caspase 3蛋白表达水平、JNK磷酸化水平以及NF-κB结合活性显著升高（均P<0.05）；与I/R组比较，B+I/R组血清CK-MB、CTnI和TNF-α水平显著下降（均P<0.05），心肌组织Cleaved caspase 8和Cleaved caspase 3蛋白表达、JNK磷酸化水平和NF-κB结合活性显著下降（均P<0.05）。结论：酒石酸布托啡诺预处理对小鼠心肌缺血再灌注损伤具有保护作用，可显著抑制I/R所致的炎症反应和心肌细胞凋亡，其机制与阻滞JNK/NF-κB信号通路相关。

Objective:To study the protective effects and it's mechanisms of butorphanol on myocardial ischemia-reperfusion injury in mice.Methods:C57BL/6 mice were randomly divided into 3 groups (10 in each group).Myocardial I/R was induced by occlusion of left anterior descending (LAD) artery for 30min,followed by reperfusion for 6h in I/R and B+I/R groups.At 30min before ischemia,butorphanol 40μg·kg^-1 was injected via the hind limb muscle in group B+I/R.While the equal volume of normal saline was injected in group sham and I/R.Blood samples were taken from the abdominal aorta to determine the concentrations of serum TNF-α,CK-MB and CTnI by ELISA.The proteins expression of Cleaved caspase 8,Cleaved caspase 3,p-JNK and JNK were detected by Western blot.The NF-κB binding activity was detected by EMSA.Results:The levels of serum CK-MB,CTnI and TNF-α were significantly higher in group I/R than those in group sham(all P<0.05).The expression of Cleaved caspase 8,Cleaved caspase 3,p-JNK,and NF-κB binding activity were also significantly increased in group I/R(all P<0.05). The levels of serum CK-MB,CTnI and TNF-α in group B+I/R were significantly reduced(all P<0.05).The expression of Cleaved caspase 8,Cleaved caspase 3,p-JNK and NF-κB were also inhibited in group B+I/R(all P<0.05).Conclusion:Butorphanol pretreatment can protect the myocardium against I/R injury in mice.The protective mechanisms of butorphanol may be through inhibiting JNK/NF-κB signaling pathway.

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