右美托咪定对小鼠全身炎性细胞因子水平的作用及其机制研究

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (3): 260-266.

右美托咪定对小鼠全身炎性细胞因子水平的作用及其机制研究

丛海涛¹，李中华²，陈斌¹，丁进峰¹，王惠琴¹，陈玲阳¹

¹温州医科大学附属浙江省台州医院麻醉科，临海 317000，浙江；²丽水市人民医院麻醉科，丽水 323000，浙江

收稿日期:2016-12-05 修回日期:2017-01-15 出版日期:2017-03-26 发布日期:2017-03-29
作者简介:丛海涛，男，硕士，副主任医师，研究方向：围术期器官保护。 Tel：13586157100 E-mail：33363534@qq.com
基金资助:
台州市科技计划资助基金（1501KY03）

Effect and mechanism of cytokine levels in mice systemic inflammation of dexmedetomidine

CONG Haitao¹, LI Zhonghua², CHEN Bin¹, DING Jinfeng1, WANG Huiqin¹, CHEN Lingyang¹

¹ Department of Anesthesiology, Taizhou Hospital of Wenzhou Medical University, Linhai 317000, Zhejiang, China;² Department of Anesthesiology, Lishui People's Hospital of Zhejiang Province, Lishui 323000, Zhejiang, China

Received:2016-12-05 Revised:2017-01-15 Online:2017-03-26 Published:2017-03-29

摘要/Abstract

摘要：

目的:本研究拟从胆碱能抗炎通路方面阐述右美托咪定的抗炎作用机制。方法: 实验动物选用BALB/c小鼠，以腹腔注射脂多糖（LPS）的方式建立内毒素血症小鼠模型，使用右美托咪定进行干预。观察动物行为学表现及进行生存率分析，实验分为三组（n=20），分别是右美托咪定组（Dex组）、生理盐水组（Saline组）、空白对组照（C组）。观察药物干预120 h后三组行为学表现及小鼠生存状况。检测血清炎症因子和观察病理形态学试验分为四组（n=16），分别为右美托咪定组（Dex组）、生理盐水组（Saline组）、α银环蛇毒素+右美托咪定组（αBGT+Dex组）、空白对照组（C组）。用酶联免疫吸附法检测血清中TNF-α、IL-1β、IL-6的浓度，最后进行病理形态学检查。颈部迷走神经切除试验分为两组（n=16）：假手术组(SHAM+Dex组)和颈部迷走神经切除组(VNX+Dex组)。注射LPS 3 h后，检测血清中TNF-α、IL-1β和IL-6的浓度。结果: 生存率分析实验中，Dex组与Saline组比较内毒素血症小鼠的生存率显著提高（P<0.01）；检测血清炎症因子试验中，Dex组血清中TNF-α、IL-1β和IL-6的水平较Saline组显著降低（P<0.01），而αBGT+Dex组血清中TNF-α、IL-1β和IL-6的水平则较Dex组显著升高（P<0.01）。并且在心脏组织、肝组织、肾组织、肺组织中病理形态有显著差异。颈部迷走神经切除试验中VNX + Dex组TNF-α、IL-1β、IL-6的表达水较SHAM + Dex组显著升高（P<0.01）。结论:本实验结果表明右美托咪定预处理显著提高内毒素血症小鼠的生存率，可能与其抑制内毒素血症小鼠血清中炎性细胞因子的表达有关。

关键词: 细胞因子, 右美托咪定, 内毒素血症

Abstract:

AIM: To elucidate the anti-inflammatory mechanism of dexmedetomidine through the cholinergic anti-inflammatory pathway. METHODS: BALB/c mice were selected as the experimental animals and were intraperitoneally injected with LPS (10 mg/kg, injection time longer than 2 min) to establish the mouse model of endotoxemia. Dexmedetomidine was applied to intervene. 60 mice were divided into three groups （20 in each）in the behavioural performance and living conditions experiment, i.e. the dexmedetomidine group (Dex group), normal saline group (Saline group) and blank control group (C group). Behavioural performance and survival rate of the three groups were observed 120 hours after drug intervention. Mice were divided into four groups with 16 in each group in the detection of serum inflammatory factors and observation of the pathological morphology, i.e. physiological saline (Saline group) and dexmedetomidine group (Dex group) alpha bungarotoxin+dexmedetomidine group (alpha BGT+Dex group) and blank control group (C group) . Enzyme linked immunosorbent assay was used to detect the concentration of serum TNF-a, IL-1β and IL-6. Pathological examination was performed thereafter. Mice were divided into two groups with 16 in each group for the cervical vagectomy experiment, i.e. sham operation group (SHAM+Dex group) and cervical vagectomy group (VNX+Dex group). Concentration of serum TNF-a, IL-1 and IL-6 three hours after LPS injection were detected.RESULTS:In the survival analysis experiment, the survival rate of dexmedetomidine group was significantly higher than that of the endotoxemia group (P<0.01). Pre-emptive administration of dexmedetomidine significantly attenuated the cytokine response after endotoxin-induced endotoxemia (P<0.01). Moreover, there were significant differences in changes of heart tissue, liver tissue, kidney tissue and lung tissue. Expression levels of TNF-a, IL-1β, IL-6 in the VNX+Dex group were significant higher than those in the SHAM + Dex group (P<0.01). CONCLUSION:Pre-emptive administration of dexmedetomidine increases the activity of cervical vagus nerve and can improve survival rate in experimental endotoxemia by inhibiting the inflammatory cytokines release.

Key words: cytokine, dexmedetomidine, endotoxemia

中图分类号:

R965.2
R614

丛海涛，李中华，陈斌，丁进峰，王惠琴，陈玲阳. 右美托咪定对小鼠全身炎性细胞因子水平的作用及其机制研究[J]. 中国临床药理学与治疗学, 2017, 22(3): 260-266.

CONG Haitao, LI Zhonghua, HEN Bin, DING Jinfeng, WANG Huiqin, CHEN Lingyang. Effect and mechanism of cytokine levels in mice systemic inflammation of dexmedetomidine[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(3): 260-266.

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