Experimental study of endomorphin-1 postconditioning against myocardial ischemia reperfusion injury in rats

Abstract

Abstract: AIM: To investigate the effects of endomorphin-1 (EM-1) postconditioning in rats on myocardial ischemia reperfusion injury.METHODS: 48 male Sprague Dawley rats were randomly divided into 8 groups:sham group (S group), ischemia-reperfusion group (IR group), ischemia postconditioning group (IPO group), EM-1 postconditioning groups (10, 20, 50 μg/kg) (EM10, EM20, EM50), EM-1 50 μg/kg+Naloxone 3 mg/kg postconditioning (EM50+Nal group), Naloxone postconditioning group (Nal group). The myocardial ischemia reperfusion injury model was established through occluding the left anterior descending branch of coronary artery for 30 min and reperfusing for 120 min in vivo. Heart rate (HR), mean arterial pressure (MAP), and Ⅱlead electrocardiogram were continuously monitored during the process. The arterial blood sample was obtained to measure plasma content of malondialdehyde(MDA) and the activities of lactate dehydrogenase (LDH), superoxide dismutase(SOD).RESULTS: In addition to the MAP of reperfusion 120 min in EM-1groups, the HR, MAP, RPP of IPO and EM-1 groups were significantly lower than IR group (P<0.05, P<0.01). Compared with IR group, the activity of LDH and content of MDA were decreased and the activity of SOD was increased (P<0.05,P<0.01) in IPO and EM-1 groups after reperfusion. EM-1 produced a dose-related effect on the content of MDA and the activity of SOD. The activity of LDH and content of MDA were higher and the activity of SOD was lower (P<0.01) in EM50+Nal group than in EM50 group after reperfusion.CONCLUSION: EM-1 postconditioning may produce the cardioprotection of myocardial ischemia reperfusion injury by activating opioid receptor, reducing the MDA and increasing the SOD.

Key words: endomorphin-1, opioid receptor, myocardial ischemia reperfusion, ischemia postconditioning, cardioprotection

CLC Number:

ZONG Qiao-feng, CHENG Xiang-yang, YU Ying, ZHANG Wei-ping, GAO Qin, LI Zheng-hong. Experimental study of endomorphin-1 postconditioning against myocardial ischemia reperfusion injury in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(2): 132-137.

References

[1] 孟玉洁,刘保江,苗永民. 阿片类药物后处理对心肌缺血再灌注损伤保护作用的研究进展[J]. 中西医结合心脑血管病杂志,2012,10(5):595-597.
[2] Zadina JE,Hackler L,Ge LJ,et al. A potent and selective endogenous agonist for the mu-opiate receptor [J]. Nature,1997,386(6624):499-502.
[3] Hui R,Wang W,Chen T,et al. Origins of endomorphin-2 immunopositive fibers and terminals in the spinal dorsal horn of the rat [J].Neuroscience,2010,169(1):422-430.
[4] Fichna J,Gach K,Perlikowska R,et al.Novel endomorphin analogues with antagonist activity at the mu-opioid receptor in the gastrointestinal tract [J].Regul Pept,2010,162(1/2/3):109-114.
[5] Anton B,Leff P,Calva JC,et al.Endomorphin 1 and endomorphin2 suppress in vitro antibody formation at ultra-low concentrations: anti-peptide antibodies but not opioid antagonists block the activity [J].Brain Behav Immun,2008,22(6):824-832.
[6] Zhou H,Hou SZ,Luo P,et al.Ginseng protects rodent hearts from acute myocardial ischemia reperfusion injury through GR/ER-activated RISK pathway in an endothelial NOS-dependent mechanism [J].J Ethnopharmacol,2011,135(2):287-298.
[7] Hausenloy DJ,Tsang A,Yellon DM. The reperfusion injury salvage kinase pathway:a common target for both ischemic preconditioning and postconditioning [J]. Trends Cardiovasc Med, 2005, 15(2):69-75.
[8] Yellon DM, Opie LH. Postconditioning for protecttion of the infarcting heart [J]. Lancet, 2006, 367(9509): 456-458.
[9] Zatta AJ,Kin H,Yoshishige D,et al. Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation [J]. Am J Physiol Heart Circ Physiol, 2008,294(3):H1444-H1451.
[10]张鹏, 朱运龙, 王跃民, 等. κ阿片受体激动剂U50488H对大鼠心肌缺血再灌注室性心律失常的影响及作用机制[J]. 中国临床药理学与治疗学,2006, 11(3):251-255.
[11]Chen Z,Li T,Zhang B. Morphine postconditioning protects against reperfusion injury in the isolated rat hearts[J]. J Surg Res,2008,145(2) : 287-294.
[12]Wong GT,Li R,Jiang LL,et al.Remifentanil post-conditioning attenuates cardiac ischemia- reperfusion injury via kappa or delta opioid receptor activation[J]. Acta Anaesthesiol Scand,2010,54(4) : 510 -518.
[13]吴云,顾尔伟,方卫平, 等. 舒芬太尼后处理对在体大鼠心肌缺血再灌注损伤的影响 [J]. 安徽医科大学学报,2011,46(7):652-655.
[14]Savateev AV,Savateeva-Liubimova TN. Apoptosis-universal mechanisms of cell death and survival in ischemia and reperfusion: ways to pharmacological control [J]. Eksp Klin Farmakol,2010,73 (12):44-49.
[15]Xia Q,Qian LB.Cardiac and cerebral ischemia/reperfusion injury and prevention strategies [J].Zhejiang Da Xue Xue Bao Yi Xue Ban,2010,39(6):551-558.
[16]章斌,许智惠,陶正贤. 血管内皮生长因子165通过抑制钙敏感性受体减少缺血/再灌注心肌细胞凋亡 [J]. 中国临床药理学与治疗学,2011,16(1):26-32.
[17]GAO YH,Chen L,Ma YL,et al. Chronic intermittent hypoxia aggravates cardiomyocyte apoptosis in rat ovariectomized model [J]. Chin Med J(Engl),2012,125(17):3087-3092.
[18]刘爱华,石孟琼,杨文雁, 等. 珠子参总皂苷对大鼠心肌缺血/再灌注损伤的保护作用及机制研究 [J]. 中国临床药理学与治疗学,2013, 18(11):1224-1232.