内吗啡肽-1对麻醉大鼠左心室功能的影响

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (8): 872-876.

内吗啡肽-1对麻醉大鼠左心室功能的影响

程向阳¹, 宗巧凤², 胡杰², 高琴², 李正红²

¹ 蚌埠医学院第一附属医院麻醉科,
² 蚌埠医学院生理学教研室,蚌埠 233000,安徽

收稿日期:2014-04-05 修回日期:2014-07-29 出版日期:2014-08-26 发布日期:2014-08-26
通讯作者: 李正红,女,教授,研究方向:心血管生理与病理生理。 Tel: 0522-3175071 E-mail: lizhbbmc@163.com
作者简介:程向阳,女,博士在读,副主任医师,研究方向:重要脏器功能保护。 Tel: 0522-3175071 E-mail: yxhyhr @163.com
基金资助:
安徽省高校省级自然科学研究重点项目(KJ2011A202); 安徽省高校省级自然科学研究项目(KJ2012Z246)

Effect of endomorphin-1 on the left ventricular function in anesthetized rats

CHENG Xiang-yang¹, ZONG Qiao-feng², HU Jie², GAO Qin², LI Zheng-hong²

¹ Department of Anesthesiology,the First Affiliated Hospital of Bengbu Medical College,;
² Department of Physiology, Bengbu Medical College, Bengbu 233000, Anhui, China

Received:2014-04-05 Revised:2014-07-29 Online:2014-08-26 Published:2014-08-26

摘要/Abstract

摘要： 目的观察内吗啡肽-1(endomorphin-1,EM-1)静脉注射和侧脑室注射对麻醉大鼠左心室功能的影响,并初步探讨其可能的作用机理。方法 Wistar大鼠麻醉后,静脉注射或侧脑室注射EM-1,经右颈总动脉左心室插管测定左心室功能,并测定血清和心肌组织NO和T-NOS含量。结果静脉注射、侧脑室注射EM-1均剂量依赖性地降低麻醉大鼠左心室功能,预先给予阿片受体阻断剂纳洛酮或特异性μ受体阻断剂cyprodime可阻断EM-1引起的心功能降低反应;预先给予胆碱能M受体阻断剂阿托品可减弱EM-1引起的心功能降低反应。静脉注射EM-1血清中NO和T-NOS比对照组有所增加,而心肌组织的NO和T-NOS无明显变化;侧脑室注射EM-1的血清和心肌组织的NO和T-NOS均无明显变化。结论静脉注射、侧脑室注射EM-1可引起麻醉大鼠在体左心室功能下降,此效应由阿片受体介导,可能有胆碱能M受体参加。

关键词: 内吗啡肽-1, 阿片受体, 左心室功能, 一氧化氮

Abstract: AIM: To observe the effects of intravenous and intracerebroventricular injection of endomorphin-1(EM-1) on the left ventricular function in anesthetized rats and to assess its mechanism. METHODS: The left ventricular function was observed by inserting a catheter from right carotid artery into left ventricle after iv or civ injection of EM-1 in anesthetized rats.The effects of iv or civ of various blockers, naloxone, cyprodime and atropine, on the left ventricular function caused by EM-1 were observed. The level of NO and T-NOS in serum and myocardial were measured.RESULTS: EM-1 was shown to decrease left ventricular function dose-dependently. The decrease in left ventricular function was blocked by naloxone and cyprodime. Pretreatment with iv or civ atropine attenuated the decrease response. Intravenous injection of EM-1 produce NO content and NOS activity in serum were much higher than those in control group (P<0.05). While NO content and NOS activity in myocardium were no more than those in control group. Intracerebroventricular injection of EM-1 produced NO content and NOS activity in serum and myocardium were no more than those in control group. CONCLUSION: iv or civ administration of EM-1 produces depressor on the left ventricular function in anesthetized rats, which is mediated by opioid receptor, associated with the Mcholinoceptor.

Key words: endomorphin-1, opioid receptor, left ventricular function, NO

中图分类号:

R965
R331

程向阳, 宗巧凤, 胡杰, 高琴, 李正红. 内吗啡肽-1对麻醉大鼠左心室功能的影响[J]. 中国临床药理学与治疗学, 2014, 19(8): 872-876.

CHENG Xiang-yang, ZONG Qiao-feng, HU Jie, GAO Qin, LI Zheng-hong. Effect of endomorphin-1 on the left ventricular function in anesthetized rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(8): 872-876.

参考文献 20

[1]	吕庆琴,陈霆隽,洪炎国.μ阿片受体的内吞抑制吗啡耐受的形成[J].中国临床药理学与治疗学,2012,17(10):1185-1190.
[2]	Zadina JE, Hackler L, Ge LJ, et al.A potent and selective endogenous against for the μ-opioid receptor[J]. Nature, 1997, 386(6624):499-502.
[3]	Hackler L, Zadina JE, Ge LJ, et al.Isolation of relatively large amounts of endomorphin-1 and endomorphin-2 from human brain cortex[J]. Pretides, 1997, 18(10):1635-1639.
[4]	Smith RR, Martin-Schild S, Kastin AJ, et al.Decreases in endomorphin-2-like immunore activity concomitant with chronic pain after nerve injury[J]. Neuroscience, 2001, 105(3):773-778.
[5]	Champion HC, Zadina JE, Kastin AJ, et al.The endogenous μ-opioid agonists endomorphin 1 and 2 have novel hypotensive activity in the rabbit[J]. Biochm Biophys Res Commun, 1997, 235(3):567-570.
[6]	Champion HC, Zadina JE, Kastin AJ, et al.Endomorphin 1 and 2 have vasodepressor activity in the anrsthetized mouse[J]. Peptides, 1998, 19(5):925-929.
[7]	Champion HC, Bivalacqua TJ, Lambert DG, et al.Endomorphin1 and 2, the endogenous mu-opioid agonists, produce biphasic changes in systemic arterial pressure in the cat[J]. Life Sci, 1998,63(9):131-136.
[8]	Kwok EH, Dun NJ.Endomorphins decrease heart rate and blood pressure possibly by activating vagal afferents in anesthetized rats[J]. Brain Res, 1998,803(1/2):204-207.
[9]	吴宁,霍笑风,陈强,等.侧脑室注射内吗啡肽-1对麻醉大鼠血压的影响[J].药学学报,2001,36(10):731-734.
[10]	陈敏,张明升,王燕,等.甘露醇对大鼠离体心脏心功能的影响[J].中国临床药理学与治疗学,2012,17(12):1368-1372.
[11]	Martin-Schild S, Gerall AA, Kastin AJ, et al.Differential distribution of endomorphin 1- and endomorphin 2-like immunoreactivities in the CNS of the rodent[J]. J Comp Neuro, 1999, 405(4):450-471.
[12]	Hayar A, Guyenet PG.Pre-and postsynaptic inhibitory actions of methionine-enkephalin on identified bulbospinal neurons of the rat RVL[J]. J Neurophysiol, 1998, 80(4):2003-2014.
[13]	Irnaten M, Aicher SA, Wang J, et al.Mu-poioid receptors are located postsynaotically and endomorphin-1 inhibits voltage-gated calcium currents in premotor cardiac parasympathetic neuros in the rat nucleus ambiguous[J]. Neuroscience, 2003, 116(2):573-582.
[14]	Wu N, Ren WH, Huo XF, et al.Effects of endomorphins and their analogs on cardiovascular system[J]. Yao-Xue-Xue-Bao, 2001, 36(4):241-245.
[15]	Qi YM, Yang DJ, Duan X, et al.Endomorphins inhibit contractile responses of rat thoracic aorta rings induced by phenylephrine and angiotensin Ⅱ in vitro[J]. Acta Pharmacol Sin, 2002, 23(1):40-44.
[16]	Champion HC, Zadina JE, Kastin AJ, et al.Endomorphin 1 and 2, endogenous ligands for the mu-opioid receptor, decrease cardiac output and total peripheral resistance in the rat[J]. Peptides, 1997, 18(9):1393-1397.
[17]	Yamazaki T, Akiykma T, Mori H.Effects of nociception on cardic norepinephrine and acetylcholine release evoked by ouabain[J]. Brain Res,2001, 904(1):153-156.
[18]	Brady AJ,Warren JB, Poole-Wilson PA, et al.Nitric oxide attenuates cardiac myocyte contraction[J]. Am J Physiol, 1993, 265(1 pt 2):H176-182.
[19]	陈猛,曾因明,段世明,等.阿芬太尼对再灌注心肌功能的保护作用及其机制[J].中国临床药理学与治疗学,2002,7(2):119-123.
[20]	Crystal GJ, Gurevicius J.Nitric oxide does not modulate myocardial contractility acutely in situ canine hearts[J]. Am J Physiol, 1996, 270(5 Pt 2)::H1568-1576.