摘 要
目的 通过以往的研究证明表示如果想缓解由于心肌受损时血量减少为避免其的二次损伤要对它进行缺血（Iscemia Postconditioning)处理。本文章就具体论述了时当给受伤缺血时的家兔注入盐酸注射液（ Oxycodone Hydrochloride Injection）后家兔的反应。本实验就是要具体探明该注射液起到的保护作用，和分析了解κ受体在经过后处理中能够产生的作用。 方法 四肢灵动，活泼康健的雄性家兔，2.5～4月龄，体重2.1～3.0k g，将家兔调整到心肌缺血并需再灌注的状态，给家兔进行开胸，并在30分钟后对左前肢进行结扎并在180分钟后进行再注射，把它们任意分成五组：1）非进行手术组（ sham组，n=8）只给左前肢穿线，并不进行结扎；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）：等再进行灌注的时候重复做三次，使得保证每次至少有30s的缺血和30s的注射； 4）后处理组（Oxpoc组，n=9）：可以在下一次注射前的五分钟左右给家兔的静脉缓慢注射(0.3mg／kg)；5）nor-binaltorphimne +后处理组（BNI+Oxpoc组，n=10）：于再灌注起始前10min给予κ受体拮抗剂nor-binaltorp
himne （3mg/kg），余处理同Oxpoc组。最后再统计数据并测出此时家兔的血清浓度，通过相关法则测出家兔已经坏死的心肌面积，并计算出所占总体面积的百分比。取一些心肌组织部分，并使用免疫组化染法的原理来检测出存在细胞缝隙中的蛋白成分，从而推导出它的平均光密度OD值是多少。
结果 与 Sham组比较，其余四组血清CK-MB、cTn-I 浓度升高（ P<0.05），I/R组、Oxpoc 组、IPOC组、 BNI+Oxpoc 组Cx43 OD 值降低（ P<0.05）；与I/R组进行比较，发现 Ipoc组和Oxpoc 组的心肌梗死面积减少，所占比例也降低了（ P<0.01），Ipoc组、 Oxpoc组血清 CK-MB、cTn-I浓度降低（ P<0.05），Ipoc组、 Oxpoc组 Cx43 OD 值升高 （ P<0.05）；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、 cTn-I 浓度升高（ P<0.05）， Cx43 OD 值降低（ P<0.05）。
结论 1. 在经过处理后能在一定程度上减轻心肌缺血的症状，它与缺血后进行心肌在注射有等同的功效。而根据κ受体拮抗剂nor-binaltorphimne 消除后产生的效果可以得出，经过的处理后，产生的保护作用的机制与κ受体是否激活有关。2.通过激活 κ阿片受体并调节 Cx43 的表达机制就有可能是产生作用的途径。
关键词：；缺血后处理；再灌注损伤；心肌；κ受体；缝隙连接蛋白43
Abstract
Objective：To evaluate the effect of oxycodone postconditioninging on myocardial Ischemia-reperfusion injury induced by myocardial ischemia-reperfusion in rabbits and the role of κopioid receptors．
Methods：Male rabbits ，aged 2～3 months,weighing 2.2～2.8 kg, establishing the model of myocardial ischemia-reperfusion injury by occlusion of the left anterior descending branch of coronary artery for 30 min followed by 180min reperfusion, were randomly divided into 5 groups using a random number table：1)sham operation group(group Sham,n=8): left anterior descending branch thread only, not ligated；2)ischemia-reperfusion group (group I／R,n=9): 30min ischemia and 180 min reperfusion only without other intervention; 3)Ischemia Post-conditioning group (group Ipoc,n=9)：At
the first three minutes of reperfusion ,three cycles of a 10s reperfusion interspersed with a 10s ischemia preceded 180min reperfusion；oxycodone postconditioning(group Oxpoc,n=9): oxycodone ,0.3mg/kg ,was injected intravenously at 5 min before reperfusion.；κreceptor antagonist nor-binaltorphimne+oxycodone postconditioning group(group BNI+ Oxpoc, n=10): BNI was given 10min prior to reperfusion and the rest of treatments as the same as Oxpoc group.
Venous blood samples were collected at the end of reperfusion for measurement of the plasma cTnI and CK-MB concentrations. The rabbits were then sacrificed and the heart tissue was adopted for the later determination. TTC staining was used to detect the myocardial infarct size and immunohistochemical staining was used to detect the expression of Cx43 protein in myocardial cells.
Results：Compared with Sham group, the plasma cTn-I and CK-MB concentrations in the other four groups were increased（ P<0.05）and the value of Cx43 OD were decreased（ P<0.05）;Compared with I/R group, Ipoc, Oxpoc area percentage reduce m
yocardial infarction group (P < 0.01), Ipoc, concentration of serum cTn -i Oxpoc group reduced (P < 0.05), Ipoc, Oxpoc Cx43 OD value (P < 0.05); Compared with I/R group, the infarct areas in Ipoc group and Oxpoc group were decreased（ P<0.01） ,the plasma cTn-I and CK-MB concentrations in Ipoc group and Oxpoc group were decreased （ P<0.05） , the value of Cx43 OD and the expression of Cx43 mRNA in Ipoc group and Oxpoc group were increased（ P<0.05） ; Compared with Ipoc group or Oxpoc group , the infarct areas, the plasma cTn-I and CK-MB concentrations were increased and the value of Cx43 OD were decreased in BNI+Oxpoc group（ P<0.05）.
Conclusions：1. Oxycodone can protect the heart from myocardial ischemia／reperfusion injury when administered at the onset of reperfusion and just as effective as ischemia post-conditioning and thc mechanism may be associated with the activation of κ receptors．2. The myocardial protection of oxycodone postconditioning may regulated the expression of Cx43 through activated κopioid receptors.
Keywords ：Oxycodone；Ischemic postconditioninging；reperfusion injury；myocardial；Connexin 43；kappa opioid receptors
中英文缩略词表
缩略词 英文全称 中文全称
I/R Ischemia reperfusion injury 缺血再灌注损伤
PCI Percutaneous coronary intervention 经皮冠状动脉介入术
TTC 2,3,5,-Triphenyl Tetrazolium chloride 氯化三苯基四氮唑
IPOC Iscemia Postconditioning 缺血后处理
