国际麻醉学与复苏杂志   2017, Issue (12): 1-1
    
联合应用α7nAChR激动剂和肢体远隔缺血后处理 对大鼠心肌缺血/再灌注损伤和炎症反应的影响
崔昕龙, 王世玉, 薛富善, 杨桂珍, 李慧娴, 刘亚洋, 廖旭1()
1.中国医学科学院整形外科医院
Cardioprotective and anti-inflammatory effects of combined α7 nicotinic acetylcholine receptor agonist and limb remote ischemic postconditioning in rats with myocardial ischemia/reperfusion injury
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摘要:

目的 探讨特异性α7亚基烟碱型乙酰胆碱受体(α7 subunit-containing nicotinic acetylcholine receptor, α7nAChR)激动剂后处理联合应用肢体远隔缺血后处理对大鼠心肌缺血/再灌注损伤(ischemia/reperfusion injury, I/RI)和炎症反应的影响。 方法 采用随机数字表法将60只雄性SD大鼠分为6组(每组10只):假手术组(S组)、对照组(C组)、缺血预处理组(IPC组)、特异性α7nAChR激动剂PNU282987后处理组(P组)、肢体远隔缺血后处理组(L组)、联合应用PNU282987后处理和肢体远隔缺血后处理组(P+L组)。监测I/R期间的HR和MAP,并计算HR和SBP乘积(rate pressure product, RPP)作为心肌氧耗指数。再灌注120 min采集静脉血样,采用ELISA法检测血清心肌肌钙蛋白I(cardiac troponin I, cTnI)、肌酸激酶心肌型同工酶(myocardial-bound creatine kinase, CK-MB)、TNF-α、IL-6、IL-10和高迁移率族蛋白1(high mobility group box 1, HMGB1)浓度;采用伊文氏蓝和氯化三苯基四氮唑双染色法测定心肌梗死面积(infarction size, IS)。 结果 与C组比较,IPC组、P组、L组和P+L组的血清cTnI 和CK-MB浓度以及IS明显降低(P<0.05);与IPC组比较,P组、L组和P+L组血清cTnI和IS明显升高(P<0.05);与P组和L组比较,P+L组的血清cTnI 和CK-MB浓度以及IS明显降低(P<0.05);与S组比较,血清TNF-α浓度在C组、IPC组和L组明显增高(P<0.05),IL-6和HMGB1浓度在C组、IPC组、P组和L组明显增高(P<0.05);与C组比较,血清TNF-α、IL-6和HMGB1浓度在IPC组、P组、L组和P+L组明显降低(P<0.05);与IPC组比较,血清TNF-α、IL-6和HMGB1浓度在P组和P+L组明显降低(P<0.05);与P组比较,血清TNF-α、IL-6和HMGB1浓度在L组明显升高(P<0.05);与L组比较,血清TNF-α、IL-6和HMGB1浓度在P+L组亦明显降低(P<0.05)。 结论 联合应用α7nAChR激动剂和肢体远隔缺血后处理可产生更强的心肌保护作用,但不增强炎症抑制作用。

关键词: 心肌; 缺血/再灌注损伤; 炎症; 胆碱能抗炎通路; 肢体远隔缺血后处理
Abstract:

Objective To assess the cardioprotective and anti-inflammatory effects of combined α7 nicotinic acetylcholine receptor(α7nAChR) agonist and limb remote ischemic postconditioning in rats with myocardial ischemia/reperfusion injury(I/RI). Methods Sixty male SD rats were randomly divided equally into six groups(n=10): sham group(S group), control group(C group), ischemia preconditioning group(IPC group), special α7nAChR agonist PNU282987 postconditioning group(P group), lime remote ischemic postconditioning group(L group), combined PNU282987 and lime remote ischemic postconditioning group(P+L group). Throughout the experiment, HR, MAP, and a lead Ⅱ electrocardiogram were continuously monitored. Blood samples were taken at 120 min of reperfusion for measuring serum concentrations of troponin I(TnI), myocardial-bound creatine kinase(CK-MB), TNF-α, high mobility group box 1 protein(HMGB-1), IL-6 and IL-10 by the kits specifically for rats. At the end of experiment, the infarct size(IS) was assessed using excised hearts by Evans blue and triphenyltetrazolium chloride staining. Results Compared with C group, the IS, serum cTnI and CK-MB concentrations were significantly decreased in IPC, P, L and P+L groups. Compared to IPC group, the IS and serum cTnI concentration were significantly higher in P, L and P+L groups. Compared to P and L groups, the IS, serum cTnI and CK-MB concentrations were significantly decreased in P+L group. At 120 min of reperfusion, serum TNF-α concentration was significantly increased in C, IPC and L groups. Also, serum IL-6 and HMGB1 concentrations were significantly increased in C, IPC, P and L groups compared with S group. Compared to C group, serum TNF-α, IL-6 and HMGB1 concentrations were significantly decreased in IPC, P, L and P+L group. Compared to IPC and L groups, serum TNF-α, IL-6 and HMGB1 concentrations were significantly decreased in P and P+L groups. Conclusions Combined α7nAChR agonist and limb remote ischemic postconditioning can provide an improved cardioprotection, but not an enhanced anti-inflammatory effect.

Key words: Myocardial; Ischemia/reperfusion injury; Inflammation; Cholinergic anti-inflammatory pathway; Limb remote ischemic postconditioning