目的 评价α7烟碱样乙酰胆碱受体(α7 nicotinic acetylcholine receptor,α7nAChR)激动剂后处理对高胆固醇血症大鼠心肌保护作用的影响。方法 采用含2%胆固醇和0.5%胆盐的饲料喂养大鼠30只,时间为8周,以诱发高胆固醇血症。采用随机数字表法将高胆固醇血症和正常大鼠分为对照组(HC组和NC组)、缺血/再灌注损伤组(HI组和NI组)和PNU282987后处理组(HPNU组和NPNU组),每组5只。检测血清总胆固醇(TC)、低密度脂蛋白(LDL)、肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI),肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平;采用伊文氏蓝和氯化三苯基四氮唑 (TTC)双重染色法测定心肌梗死面积。结果 与NC组比较,HC组TC和LDL明显升高(P<0.05);与NI组比较, NPNU组血清CKMB和cTnI水平明显降低,血清TNF-α和IL-6水平明显降低,心肌梗死面积明显缩小(P<0.05)。与HI组比较,HPNU组血清CKMB、cTnI、TNF-α和IL-6水平、心肌梗死面积比较差异均无统计学意义。结论 高胆固醇血症可明显加重心肌缺血/再灌注损伤,并消除α7nAChR激动剂后处理的心肌保护作用。
Abstract
Objective To evaluate the effect of postconditioning with α7 nicotinic acetylcholine receptor (α7nAChR) agonist on myocardial protection in hypercholesterolemic rats.Methods A hypercholesterolemic model of rats was induced by means of a eight-week diet containing 2% cholesterol and 0.5% bile salts. Hypercholesterolemic and normal rats were randomly divided into three groups respectively (n=5): control group (group HC and NC), ischemia/reperfusion injury group (group HI and NI), and PNU282987 postconditioning group (group HPNU and NPNU). Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), creatine kinase MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor (TNF) -α and interleukin (IL) -6 were assayed. The size of myocardial infarction was determined by Evans blue and triphenyltetrazolium chloride (TTC) staining.Results Compared with group NC, levels of TC and LDL were elevated significantly in group HC (P<0.05). Compared with group NI, serum levels of CKMB, cTnI, TNF-α, IL-6, and myocardial infarct size were decreased significantly in group NPNU (P<0.05). No significant difference was found between group HI and group HPNU (P>0.05).Conclusions Hypercholesterolemia can aggravate myocardial ischemia/reperfusion injury and eliminate the myocardial protective effect of α7nAChR agonist postconditioning against myocardial ischemia/reperfusion injury.
关键词
缺血/再灌注损伤 /
高胆固醇血症 /
心肌保护
Key words
ischemia/reperfusion injury /
hypercholesterolemia /
cardioprotection
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基金
国家自然科学基金(81470019);中国医学科学院整形外科医院院所青年创新基金(Q2017002)
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