κ受体参与羟考酮后处理对家兔心肌缺血再灌注损伤的保护

发布时间：2018-12-13 23:44

【摘要】：目的:既往研究结果显示缺血后处理(Iscemia Postconditioning)能够减轻心肌缺血再灌注损伤。本实验旨在探明盐酸羟考酮注射液(Oxycodone Hydrochloride Injection)用于后处理是否产生上述保护效应,以及了解κ受体在羟考酮后处理中的作用。方法:健康雄性家兔,2~3月龄,体重2.2~2.8 k g,建立心肌缺血再灌注损伤模型,家兔开胸后左前降支给予30min结扎和180min再灌注,随机分为5组:1)假手术组(sham组,n=8)左前降支只穿线,不结扎;2)缺血再灌注组(I/R组,n=9):左前降支结扎心肌缺血30 min,再灌注180 min;3)缺血后处理组(Ipoc组,n=9):再灌注起始3min内给予重复3次的30s缺血/30s再灌;4)羟考酮后处理组(Oxpoc组,n=9):再灌注起始前5min开始缓慢静脉给予羟考酮(0.3mg/kg);5)nor-binaltorphimne+羟考酮后处理组(BNI+Oxpoc组,n=10):再灌注起始前10min给予κ受体拮抗剂nor-binaltorphimne(3mg/kg),余处理同Oxpoc组。再灌注末测定血清cTnI浓度、TTC法测定心肌梗死面积,计算心肌梗死面积百分比(IS/LV)。留取心肌组织,免疫组化染色法检测细胞缝隙连接蛋白43(CX43蛋白)的表达,计算其平均光密度OD值。结果:与Sham组比较,其余四组血清CK-MB、cTn-I浓度升高(P0.05),Cx43OD值降低(P0.05);与I/R组比较,Ipoc组、Oxpoc组心肌梗死面积百分比、血清CK-MB、cTnI浓度降低(P0.05),Ipoc组、Oxpoc组Cx43 OD值升高(P0.05);与Ipoc组或Oxpoc组比较,BNI+Oxpoc组心肌梗死面积百分比和血清CK-MB、cTnI浓度升高(P0.05),Cx43 OD值降低(P0.05)。结论:1.羟考酮后处理具有与缺血后处理同等程度的减轻心肌缺血再灌注损伤作用。2.羟考酮后处理心肌保护作用的机制与κ受体的激活有关。3.羟考酮后处理可能通过激动κ阿片受体改善Cx43的表达与分布发挥心肌保护作用。
[Abstract]:Objective: previous studies have shown that post-ischemic (Iscemia Postconditioning) can reduce myocardial ischemia-reperfusion injury. The purpose of this study was to investigate the protective effect of hydroxycodone hydrochloride injection (Oxycodone Hydrochloride Injection) and the role of 魏 receptor in hydroxycodone aftertreatment. Methods: the model of myocardial ischemia reperfusion injury was established in healthy male rabbits, aged 2 to 3 months and weighing 2.2 ~ 2.8 kg. The left anterior descending branch was ligated with 30min and 180min reperfusion. The rabbits were randomly divided into 5 groups: 1) sham-operation group (sham group); The left anterior descending branch was only threaded and not ligated; 2) Ischemia-reperfusion group (I / R group, n / 9): left anterior descending branch ligated myocardial ischemia for 30 min, and reperfusion for 180 min;3) Ipoc group (n = 9): repeated 30 s ischemia / 30 s reperfusion in the initial 3min of reperfusion; 4) hydroxycodone post-treatment group (Oxpoc group, n = 9): 5min was given 0.3mg/kg slowly before reperfusion. 5) (BNI Oxpoc group (n = 10): 10min was given 魏 receptor antagonist nor-binaltorphimne (3mg/kg) before reperfusion, and the rest was treated with Oxpoc group. Serum cTnI concentration was measured at the end of reperfusion, myocardial infarction area was measured by TTC method and myocardial infarction area percentage (IS/LV) was calculated. The expression of gap junction protein 43 (CX43 protein) was detected by immunohistochemical staining and the mean optical density (OD) was calculated. Results: compared with the Sham group, the serum CK-MB,cTn-I concentration in the other four groups increased (P0.05) and the Cx43OD value decreased (P0.05). Compared with I / R group, the percentage of myocardial infarction size and serum CK-MB,cTnI concentration in Ipoc group and Oxpoc group decreased (P0.05), Ipoc group, Oxpoc group increased Cx43 OD value (P0.05); Compared with Ipoc group or Oxpoc group, the percentage of myocardial infarction area and serum CK-MB,cTnI concentration in, BNI Oxpoc group increased (P0.05), Cx43 OD value decreased (P0.05). Conclusion: 1. Hydroxycodone post-treatment has the same effect of alleviating myocardial ischemia-reperfusion injury as after-ischemia treatment. 2. 2. The mechanism of myocardial protection induced by hydroxycodone is related to the activation of 魏 receptor. 3. 3. Hydroxycodone postconditioning may improve the expression and distribution of Cx43 through activation of 魏 opioid receptor.
【学位授予单位】：河北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R542.22

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