纳洛酮治疗小鼠柯萨奇病毒诱发病毒性心肌炎的实验研究

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (12): 1340-1346.

纳洛酮治疗小鼠柯萨奇病毒诱发病毒性心肌炎的实验研究

丁媛媛¹, 王淑梅², 赵钢涛¹, 杨凡¹, 王四旺³

¹北京军区总医院药理科, 北京 100700;
²北京军区总医院体检中心, 北京 100700;
³第四军医大学药物研究所, 西安 710032, 陕西

收稿日期:2009-09-21 修回日期:2009-10-19 发布日期:2020-10-20
作者简介:丁媛媛, 女, 药师, 研究方向:治疗病毒性心肌炎的新药研究。Tel:010-66721898 　E-mai l:dyymiss@yahoo .com.cn
基金资助:
国家自然科学基金资助项目( 20872180); 陕西省中医药管理局资助项目( 2007042)

Experimental study on effect of naloxone on viral myocarditis caused by coxsackievirus B₃ in mice

DING Yuan-yuan¹, WANG Shu-mei², ZHAO Gang-tao¹, YANG Fan¹, WANG Si-wang³

¹Department of Pharmacology, General Hospital of Beijing Military Command, Beijing 100700, China;
²Medical Examination Center of Beijing Military Command, Beijing 100700, China;
³Institute of Madteria Medical, the Fourth Military Medical University, Xi'an 710032, Shaanxi, China

Received:2009-09-21 Revised:2009-10-19 Published:2020-10-20

摘要/Abstract

摘要： 目的：研究纳洛酮治疗病毒性心肌炎( viral myocarditis, VMC) 小鼠的作用机制。方法：120 只BALB/c 小鼠以柯萨奇病毒( coxsackievirus B₃,CVB₃) 诱导制作VMC 模型, 在隔离实验室饲养。分别在接种病毒后72 h 各组给药至21 d, CVB₃组i.p.2500 mg/kg 生理盐水( n =60);纳络酮组i.p.2 mg/kg( n =60);另取40 只BALB/c 小鼠作为对照组, 同法接种100 μL 不含病毒的Eagle 液,72 h 后i.p.给予2500 mg/kg 生理盐水。在病毒感染第5 、7 、14 、21 、28 天, 各组随机取8 只小鼠,处死, 留取心肌组织。观察小鼠死亡率与心肌组织病理改变, 并采用RT-PCR 和Western blot 技术检测CVB₃ 感染后各时间点小鼠心肌组织中κ-阿片受体( κ-opioid receptor, κOR) mRNA 和蛋白质的表达水平。结果：CVB₃ 感染后第5 、7 、14 、21 天,CVB₃ 组κOR mRNA 表达量显著高于对照组( P <0.01);κOR 蛋白质的表达量在CVB₃感染后第7 、14 、21 天明显高于对照组( P <0.05) 。CVB₃感染后第7 、14 、21 天纳洛酮组小鼠死亡率和病理组织改变低于CVB₃组, κOR mRNA 和蛋白质的表达量低于CVB₃组( P <0.05) 。结论：CVB₃诱导性VMC小鼠心肌细胞的κOR 基因和蛋白质水平明显上调, 纳洛酮对VMC 小鼠保护作用与抑制κOR 基因和蛋白质水平有关。

关键词: κ-阿片受体;, 病毒性心肌炎, 纳洛酮

Abstract: AIM: To investigate the mechanism of naloxone on mice viral myocarditis caused by coxsackievirus B₃( CVB₃ ).METHODS: 120 mice were randomly divided according to experiment protocol and inoculated intraperitoneally with CVB₃ ( 100 ×TCID₅₀ ) 0.1mL.72 h after viral inoculation, 40 of the inoculated mice were given naloxone i.p.2 mg/kg for 21 days.Another 40 inoculated mice were treated with i.p.0.9 % NaCl solution daily and were as CVB3 group.Mice without inoculation ( n =40) were given i.p.0.9 % NaCl solution daily and used as normal controls.Mice were executed, and hearts were collected on Days 5, 7, 14, 21 and 28.The death rate and pathological examination were evaluated.RT-PCR technique and Western Blot technique were used to investigate the changes of expression of κOR mRNA and protein in mice at different time points during VMC with CVB3 infection.RESULTS: On the 5, 7, 14, 21 day after viral infection, the expression of κOR mRNA was dramatically increased in the myocardium of VMC mice( P <0.01).On the 7, 14, 21 day after viral infection, the expression of κOR protein in myocardium of VMC mice was dramatically increased( P <0.05). The death rate in the naloxone group ( 50 %, n =20) was significantly lower than that in the CVB₃group ( 75 %, n =20);On the 7, 14, 21 day after viral infection, the changes of pathological and expression of κOR mRNA and protein in myocardium of naloxone group were dramatically lower than those in the CVB3 group( P <0.05).CONCLUSION: The up-regulation of κOR gene and protein were observed at different times during VMC.Naloxone can significantly improve the effectiveness in the treatment of VMC by inhibiting the up-regulation of κOR gene and protein.

Key words: κ-opioid receptor;, viral myocarditis, naloxone

中图分类号:

R965.2

丁媛媛, 王淑梅, 赵钢涛, 杨凡, 王四旺. 纳洛酮治疗小鼠柯萨奇病毒诱发病毒性心肌炎的实验研究[J]. 中国临床药理学与治疗学, 2009, 14(12): 1340-1346.

DING Yuan-yuan, WANG Shu-mei, ZHAO Gang-tao, YANG Fan, WANG Si-wang. Experimental study on effect of naloxone on viral myocarditis caused by coxsackievirus B₃ in mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(12): 1340-1346.

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