Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3
Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3
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尼古丁抑制柯萨奇病毒 B3 感染小鼠促炎细胞因子的产生
DOI：
10.1016/j.lfs.2016.02.003
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发表时间：
2016-03-01
期刊：
影响因子：
6.1
通讯作者：
Li Yue-Chun
中科院分区：
文献类型：
--
作者：
Ge Li-Sha;Zhao Jing-Lin;Li Yue-Chun
目的：尽管在病毒性心肌炎中交感神经过度激活以及用β受体阻滞剂抑制交感神经的保护作用已明确，但增强迷走神经张力对病毒性心肌炎的影响仍不清楚。在一些模型中，已证实使用α7烟碱型乙酰胆碱受体（α7 - nAChR）激动剂激活迷走神经可改善炎症。因此，本研究旨在检验使用α7 - nAChR激动剂尼古丁对急性病毒性心肌炎小鼠模型进行胆碱能刺激的效果。
材料与方法：BALB/C小鼠通过腹腔注射柯萨奇病毒B3感染。尼古丁和甲基牛扁碱（一种α7 - nAChR拮抗剂）分别以0.4 mg/kg和0.8 mg/kg的剂量，每天给药3次，连续给药7天或14天。研究尼古丁和甲基牛扁碱对存活率、心肌组织病理学变化、心功能、细胞因子水平、病毒RNA、丙二醛以及超氧化物歧化酶含量的影响。
主要发现：与甲基牛扁碱相比，尼古丁显著提高了感染小鼠的存活率，减轻了心肌炎症，并改善了柯萨奇病毒B3诱导的小鼠心肌炎中左心室功能的损害。与甲基牛扁碱相比，用尼古丁治疗的感染小鼠中促炎细胞因子肿瘤坏死因子 - α、白细胞介素 - 1β、白细胞介素 - 6和白细胞介素 - 17A显著降低。尼古丁对柯萨奇病毒B3感染的小鼠没有显著的抗氧化和抗病毒作用。
意义：结果表明，尼古丁的胆碱能刺激显著降低了小鼠病毒性心肌炎的严重程度。这些发现提示α7 nAChR激动剂可能是心肌炎患者一种有前景的新策略。（C）2016爱思唯尔公司。保留所有权利。
Aims: Although excessive sympathetic activation in viral myocarditis and the protective effects of sympathetic inhibition with beta-blockers are clear, the effects of enhancing vagal tone on viral myocarditis remain unclear. In several models, vagus nerve activation with the alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR) agonists has been demonstrated to ameliorate inflammation. This study was therefore designed to examine the effects of cholinergic stimulation with alpha 7-nAChR agonist nicotine in a murine model of acute viral myocarditis.Materials and methods: BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine and methyllycaconitine (an alpha 7-nAChR antagonist) were administered at doses of 0.4 mg/kg and 0.8 mg/kg three times per day for 7 or 14 consecutive days, respectively. The effects of nicotine and methyllycaconitine on survival rate, myocardial histopathological changes, cardiac function, cytokine levels, viral RNA, malondialdehyde, and superoxide dismutase contents were investigated.Key findings: Nicotine significantly increased survival rate of the infected mice, decreased myocardial inflammation, and improved the impairment of left ventricular function in murine coxsackievirus B3-induced myocarditis compared with methyllycaconitine. The proinflammatory cytokines TNF-alpha, IL-1 beta, IL-6 and IL-17A were significantly decreased in the infected mice treated with nicotine compared with methyllycaconitine. Nicotine had no significant anti-oxidative and antiviral effects in coxsackievirus B3-infected mice.Significance: The results indicate that cholinergic stimulation with nicotine significantly reduced the severity of viral myocarditis in mice. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with myocarditis. (C) 2016 Elsevier Inc. All rights reserved.