Wu Yun, Wan Jing, Zhen Wen-Zhon, Chen Liu-Fang, Zhan Jia, Ke Jian-Juan, Zhang Zong-Ze, Wang Yan-Lin
Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Interact Cardiovasc Thorac Surg. 2014 Mar;18(3):308-12. doi: 10.1093/icvts/ivt516. Epub 2013 Dec 13.
Butorphanol tartrate is a synthetic opioid partial agonist analgesic. Butorphanol targets the heart, mainly via κ-opioid receptor (κ-OR) activation. The purpose of this study was to determine the effect and mechanism underlying butorphanol postconditioning (B-Post) on myocardial ischaemia reperfusion injury in rats.
Seventy-five male Sprague-Dawley rats were randomly divided into five groups of 15 each: Group sham; Group I/R (ischaemia/reperfusion); Group B (butorphanol postconditioning); Group B/N (butorphanol postconditioning + antagonist of κ-OR nor-binaltorphimine [Nor-BNI]); Group B/G (butorphanol postconditioning + nonselective ATP-sensitive potassium (KATP) channel blocker glibenclamide [GLI]). The left coronary anterior descending artery (LAD) was occluded for 30 min, followed by a 120-min reperfusion. Blood samples were obtained at the end of reperfusion for determination of serum tumour necrosis factor (TNF)-α and interleukin (IL)-6 concentrations. The hearts were then excised for determination of myocardial infarct size by triphenyltetrazolium chloride staining. The myocardial tissues were used for determination of the expression of myocardial superoxide dismutase (SOD), malondialdehyde (MDA) and myeloperoxidase (MPO).
Myocardial infarct size was significantly reduced in B (26.4 ± 1.83%), B/N (34.5 ± 1.56%) and B/G (31.5 ± 1.27%) Groups compared with Group I/R (46.8 ± 1.41%) (all P < 0. 001). The serum TNF-α and IL-6 concentrations and the MDA and MPO activities in the ischaemic area in B, B/N and B/G Groups were significantly lower than those in the I/R Group (all P < 0.001). In addition, myocardial infarct size, TNF-α and IL-6 concentrations and the MDA and MPO activities in B/N and B/G Groups were higher than those in the B Group (all P < 0.001). In contrast, SOD activity was significantly increased in B, B/N and B/G Groups, and SOD activity in B/N and B/G Groups was less than in the B Group (all P < 0.001).
These results suggest that postconditioning of butorphanol tartrate can provide a potent cardioprotective effect against myocardial ischaemic and reperfusion injury. Both the κ-OR and the KATP channels were involved in this effect.
酒石酸布托啡诺是一种合成阿片类部分激动剂镇痛药。布托啡诺主要通过激活κ-阿片受体(κ-OR)作用于心脏。本研究旨在确定布托啡诺后处理(B-Post)对大鼠心肌缺血再灌注损伤的影响及机制。
75只雄性Sprague-Dawley大鼠随机分为5组,每组15只:假手术组;缺血/再灌注组(I/R);布托啡诺后处理组(B组);布托啡诺后处理+κ-OR拮抗剂诺-纳曲酮(Nor-BNI)组(B/N组);布托啡诺后处理+非选择性ATP敏感性钾(KATP)通道阻滞剂格列本脲(GLI)组(B/G组)。结扎左冠状动脉前降支30分钟,然后再灌注120分钟。再灌注结束时采集血样,测定血清肿瘤坏死因子(TNF)-α和白细胞介素(IL)-6浓度。然后取出心脏,用氯化三苯基四氮唑染色法测定心肌梗死面积。心肌组织用于测定心肌超氧化物歧化酶(SOD)、丙二醛(MDA)和髓过氧化物酶(MPO)的表达。
与I/R组(46.8±1.41%)相比,B组(26.4±1.83%)、B/N组(34.5±1.56%)和B/G组(31.5±1.27%)的心肌梗死面积显著减小(均P<0.001)。B组、B/N组和B/G组缺血区血清TNF-α和IL-6浓度以及MDA和MPO活性均显著低于I/R组(均P<0.001)。此外,B/N组和B/G组的心肌梗死面积、TNF-α和IL-6浓度以及MDA和MPO活性均高于B组(均P<0.001)。相反,B组、B/N组和B/G组的SOD活性显著增加,B/N组和B/G组的SOD活性低于B组(均P<0.001)。
这些结果表明,酒石酸布托啡诺后处理可对心肌缺血再灌注损伤提供有效的心脏保护作用。κ-OR和KATP通道均参与了这一作用。