Role of μ opioid receptor in morphine preconditioning-induced reduction of myocardial ischemia-reperfusion injury in rats with chronic heart failure: an in vitro experiment
10.3760/cma.j.issn.0254-1416.2018.05.026
- VernacularTitle:μ受体在吗啡预处理减轻慢性心力衰竭大鼠心肌缺血再灌注损伤中的作用:离体实验
- Author:
Shiyun JIN
1
;
Shufang HE
;
Jun HUANG
;
Jinzhong CHAN
;
Yonglu PAN
;
Ye ZHANG
Author Information
1. 230601,安徽医科大学第二附属医院麻醉科
- Keywords:
Morphine;
Receptors,opioid,mu;
Heart failure;
Myocardial reperfusion injury
- From:
Chinese Journal of Anesthesiology
2018;38(5):606-609
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of μ opioid receptor in morphine preconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in rats with chronic heart failure.Methods Adult male Sprague-Dawley rats,weighing 170-230 g,in which chronic heart failure was induced by injecting doxorubicin via the tail vein,were studied.The rats were sacrificed and their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 37 ℃.Forty isolated rat hearts with I/R injury were randomly divided into 4 groups (n=10 each):group I/R,morphine preconditioning group (group MP),μ opioid receptor antagonist CTOP plus morphine preconditioning group (group CTOP+MP) and CTOP group.Myocardial I/R was induced by occlusion of the left coronary artery for 30 min followed by 120 min of reperfusion.In group MP,the hearts were perfused with K-H solution for 15 min,with K-H solution containing 1 μmol/L morphine for 5 min and with K-H solution for 5 min,3 cycles in total,and then the model of myocardial I/R was established.The hearts were perfused with K-H solution containing 1 μmol/L CTOP starting from 10 min before morphine preconditioning until 5 min of ischemia in group CTOP + MP.The hearts were perfused with K-H solution containing 1 μmol/L CTOP starting from 40 min before ischemia until 5 min of ischemia in group CTOP.The coronary effluent was collected at 15 min of equilibration (baseline) and 5 and 10 min of reperfusion to detect the activity of lactate dehydrogenase (LDH).Myocardial infarct size (IS) and the area at risk (AAR) were measured by 2,3,5-triphenyl-tetrazolium staining,and IS/AAR percentage was calculated.The expression of Bcl-2 and Bax mRNA was determined using uantitative real-time polymerase chain reaction,and the ratio of Bcl-2/Bax was calculated.Results Compared with group I/R,the IS and IS/AAR percentage were significantly decreased,the activity of LDH in coronary effluent was decreased,the expression of Bax mRNA was downregulated,the expression of Bcl-2 mRNA was up-regulated,and the Bcl-2/Bax ratio was increased in group MP (P＜0.05),and no significant change was found in the IS or IS/AAR percentage in CTOP and CTOP+ MP groups (P＞0.05).Compared with group MP,the IS and IS/AAR percentage were significantly increased,the activity of LDH in coronary effluent was increased,the expression of Bax mRNA was up-regulated,the expression of Bcl-2 mRNA was down-regulated,and the Bcl-2/Bax ratio was decreased in group CTOP+MP (P＜0.05).Conclusion The mechanism by which morphine preconditioning reduces myocardial I/R injury may be related to activating μ opioid receptors and thus maintaining the balance between Bcl2 and Bax gene expression in the rats with chronic heart failure.
