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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2011年第1期

页码:

35-38

栏目:

基础研究

出版日期:

2010-10-27

文章信息/Info

Title:

The regulation of к-opioid receptor stimulation on the expression of Cx43 gene and its protein in myocardium

作者:

田菲¹; 2; 3; 黄秋菊⁴; 王微¹; 张权宇¹; 李娟¹; 朱霞³; 裴建明¹

第四军医大学:1.基础部生理学教研室，2.基础部教学实验中心，3.航空航天医学系心理学教研室，西安 710032；4.离休退休干部休养所卫生所，陕西 宝鸡 721001

Author(s):

TIAN Fei¹; 2; 3;  HUANG Qiu-ju⁴;  WANG Wei¹;  ZHANG Quan-yu¹;  LI Juan¹;  ZHU Xia²;  PEI Jian-ming¹

1.Department of Physiology, 2.Center of Teaching and Experimentation, 3.Department of Psychology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China; 4.Clinic, Baoji Sanatorium for Retired Cadres, Baoji 721001, Shaanxi, China

关键词:

κ阿片受体; β肾上腺素受体; U50; 488H; 异丙肾上腺素; Cx43; 大鼠

Keywords:

κopioid receptor;  β adrenergic receptor;  U50; 488H;  isopreterenol;  Cx43;  rat

分类号:

Q577

DOI:

-

文献标识码:

A

摘要:

目的: 探讨心脏κ阿片受体对心肌Cx43基因和其蛋白表达的调节作用。方法： 将35只成年雄性SD大鼠随机进行实验分组。大鼠麻醉后，经股静脉分别给于κ阿片受体和β肾上腺素受体的激动剂或阻断剂。30 min后，剪取左心室心肌组织，用RT-PCR技术检测大鼠心肌组织中Cx43 mRNA的表达水平。用免疫组化染色法检测Cx43总蛋白和磷酸化的Cx43蛋白(P-Cx43)的表达。结果： κ阿片受体激动剂U50,488H可使Cx43 mRNA的表达明显降低；而β肾上腺素受体激动剂异丙肾上腺素可明显提高Cx43 mRNA的表达（P<0.05）。β肾上腺素受体阻断剂普萘洛尔和κ阿片受体激动剂U50,488H均可明显抑制异丙肾上腺素的上述作用。异丙肾上腺素可使P-Cx43的表达降低；而普萘洛尔和U50,488H则可抑制异丙肾上腺素所致P-Cx43表达的降低。上述U50,488H的作用均可被κ阿片受体选择性阻断剂Nor-BNI所阻断。结论： κ阿片受体可通过影响β肾上腺素受体进而调节Cx43的功能。

Abstract:

AIM: To explore the effects and mechanism of κ opioid receptor and β adrenergic receptor stimulation on the expression of Cx43 gene and its protein in myocardium. METHODS: 40 male SD rats (250±20) g were randomly divided into different groups. Animals were given different agents according to experimental condition including κ opioid receptor and β adrenergic receptor agonist and antagonist. After 30 min, the left ventricular tissue was adopted for the later determination. RT-PCR was used to detect the amount of Cx43 mRNA and an immunohistochemical staining was used to detect the expression of Cx43 protein in myocardial cells. RESULTS: Compared with the control, the expression of Cx43 mRNA decreased with administration of U50,488H (a selective κ opioid receptor agonist), while increased with administration of isoproterenol, a β adrenergic receptor agonist. Meanwhile, U50,488H and propranolol, a non-specific β adrenergic receptor antagonist, inhibited the increased expression of Cx43 mRNA induced by isoproterenol(P<0.05). Accordingly, compared with control, the phosphorylated Cx43 protein was decreased with administration of isopreterenol. Meanwhile, both U50,488H and propranolol inhibited the decreased expression of phosphorylated Cx43 induced by isoproterenol. CONCLUSION: κ opioid receptor agonist U50,488H affects cardiac Cx43 expression via inhibiting β-adrenergic receptor signaling pathway.

参考文献/References

[1]Liu JC , Yin W, Yin Z, et al. Anti-arrhythmic effects of kappa-opioid receptor and its changes in ischemia and reperfusion [J]. Arch Med Res, 2008, 39(5):483-488.

[2]殷召，张权宇，王跃民，等. 连接蛋白43表达的变化与心律失常的关系[J]. 心脏杂志， 2008， 20(2)：244-247.

[3]姚青,王跃民,张鹏,等. к阿片受体介导的抗心律失常作用[J]. 心脏杂志, 2004, 16(2):109-112.

[4]张鹏,朱运龙,王跃民,等. к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[J]. 第四军医大学学报, 2004, 25(18):1648-1651.

[5]Pei JM, Bi H, Wang YM, et al. β-adrenergic response modulated by K-opioid receptor stimulation is attenuated following chronic hypoxia[J]. J Med Coll PLA, 2003, 18(1):1-7.

[6]Severs NJ, Bruce AF, Dupont E, et al. Remodelling of gap junctions and connexin expression in diseased myocardium[J]. Cardiovasc Res, 2008, 80(1):9-19.

[7] Bian JS, Zhang WM, Pei JM, et al. The role of phosphodiesterase in mediating the effect of protein kinase C on cyclic AMP accumulation upon kappa-opioid receptor stimulation in the rat heart[J]. J Pharmacol Exp Ther, 2000, 292(3):1065-1070.

备注/Memo

备注/Memo:

收稿日期：2010-07-26.基金项目：国家自然科学基金项目资助（30770802, 30971060) 通讯作者：裴建明，教授，主要从事阿片受体心脏保护的研究Email:jmpei8@fmmu.edu.cn 共同通讯作者：朱霞，副教授，主要从事航空心理学的研究Email:zhuxia@fmmu.edu.cn 作者简介：田菲，硕士生Email:281568830@qq.com

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更新日期/Last Update: 2010-10-27