摘要
目的评价吗啡后处理对大鼠离体心脏缺血再灌注损伤的影响。方法雄性SD大鼠,体重180~200g,应用Langendorff灌流装置,采用全心停灌45min、再灌注60min的方法制备大鼠离体心脏缺血再灌注模型。实验一:取模型制备成功的心脏32个,随机分为4组(n=8):Ⅰ组~Ⅳ组,Ⅰ组不予处理,Ⅱ组-Ⅳ组于再灌注即刻分别灌注含0.3、3.0和30μmol/L吗啡的K-H液10min,随后灌注正常K—H液50min;实验二:根据实验一的结果,选择对离体心脏缺血再灌注损伤影响最强的吗啡浓度,另取模型制备成功的心脏32个,随机分为4组(n=8):Ⅰ组~Ⅳ组,Ⅰ组不予处理,Ⅱ组~Ⅳ组于再灌注即刻分别灌注含吗啡的K—H液5、10和20min,随后灌注正常K-H液50min;实验三:根据实验二的结果,选取对离体心脏缺血再灌注损伤影响最强的吗啡后处理方法。另取模型制备成功的心脏37个,随机分为5组:Ⅰ组(n=8)不予处理;Ⅱ组(n=8)、Ⅲ组-Ⅴ组(n=7)于再灌注即刻分别灌注含吗啡、10μmol/L非选择性阿片受体阻断剂纳洛酮和吗啡、5μmol/L选择性κ受体阻断剂nor-binahorphimine和吗啡、5μmol/L选择性8受体阻断剂naltrindole和吗啡的K-H液,各组均再灌注正常K-H液50min。于再灌注60min时测定心肌肌酸激酶同工酶(CK-MB)活性,计算心肌缺血危险区,梗塞区(IS/AAR)。结果根据实验一、二的结果于再灌注即刻灌注含3.0μmol/L吗啡的K-H液10min行后处理。实验三的结果:与Ⅰ组比较,Ⅱ组和Ⅴ组心肌IS/AAR和CK—MB活性降低,Ⅳ组心肌CK-MB活性降低(P〈0.05或0.01),Ⅲ组以上指标差异无统计学意义(P〉0.05);与Ⅱ组比较,Ⅲ组和Ⅳ组心肌IS/AAR和CK-MB活性升高(P〈0.01),Ⅴ组上述指标差异无统计学意义(P〉0.05)。结论吗啡后处理可减轻大鼠离体心脏缺血再灌注损伤,此作用可能与激活心肌κ受体有关。
Objective To determine whether morphine postconditioning (MP) could protect the heart against ischemia reperfusion (I/R) injury and which specific type(s) of the opioid receptor is involved in the cardioprotective effect produced by MP. Methods Male SD rats weighing 180-200 g were killed after intraperitoneal heparin 500 U/kg. The hearts were immediately removed and passively perfused in a Langendorff apparatus with K-H solution gassed with 95% 02-5% CO2. HR and left ventricular systolic pressure (LVSP) were measured from a fluid-filled latex balloon in the left ventricle. Global myocardial ischemia was induced by interrupting perfusion for 45 min followed by 60 min reperfusion. The experiment was performed in 3 parts : In Part Ⅰ 32 isolated rat hearts were randomly divided into 4 groups (n = 8 each): group Ⅰcontrol received no treatment; group Ⅱ , Ⅲ , Ⅳ were first perfused with K-H solution containing morphine 0.3, 3.0 and 30 μmol/L respectively for 10 min immediately after the end of ischemia followed by 50 min normal K-H solution perfusion. In part Ⅱ , the concentration of morphine in K-H solution which provided the best cardio-protective effects was chosen according to the result of Part Ⅰ. , 32 isolated rat hearts were randomly divided into 4 groups ( n = 8 each) : group Ⅰ received no treatment; group Ⅱ ,Ⅲ , Ⅳ were first perfused with K-H solution containing morphine for 5, 10, 20 min respectively immediately after ischemia followed by 50 min perfusion with normal K-H solution. In part Ⅲ, the MP method which provided the best cardio-proteetive effects was chosen according to the result of PartⅡ , 37 isolated rat hearts were randomly divided into 5 groups : group Ⅰ control ( n = 8) ; group n - Ⅴ were first perfused for 10 min with K-H solution containing morphine ( Ⅱ, n = 8)/morphine + naloxone 10 μmol/L( Ⅲ , n = 7)/ morphine + nor-binahorphimine 5μmol/L (specific κ receptor antagonist, n = 7 )/morphine + naltrindole 5 μmol/L (specific δ receptor antagonist, n = 7 ) followed by 50 min reperfusion with normal K-H solution. Myocardial CK-MB activity was measured and myocardial infarct size (IS/AAR) determined (by 2,3,5-triphenyl tetrazolium staining) at the end of 60 min reperfusion. Results The postconditioning with morphine 3.0 μmol/L perfusion for 10 min provided the best cardio-proteetive effects in terms of IS/AAR and myocardial release of CK-MB. Naloxone completely abolished the cardio-protective effects of MP. Nor-binahorphimine partly reversed the protective effect of MP, while naltrindole had no effects on MP. Conclusion MP protects the heart against I/R injury via activating κ receptor.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2009年第2期111-114,共4页
Chinese Journal of Anesthesiology
关键词
吗啡
心肌再灌注损伤
缺血后处理
Morphine
Myocardial reperfusion injury
Postconditioning