芪龙通络颗粒对啮齿动物的镇痛、镇静作用及抗偏头痛机制的评价

Evaluation of analgesic, sedative effects and antimigraine mechanism of Qilong Toutong Granule () in rodents.

作者信息

Wu Xiao-Fang, Zhang Mei-Kui, Huang Huai

机构信息

Department of Encephalopathy, The First Hospital of Hunan University of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China.

出版信息

Chin J Integr Med. 2014 Apr 16. doi: 10.1007/s11655-014-1811-9.

DOI:10.1007/s11655-014-1811-9

PMID:24740554

Abstract

OBJECTIVE

To evaluate the analgesic and sedative effects of Qilong Toutong Granule (, QTG) and explore its possible mechanisms.

METHODS

Kunming mice were randomly divided into 6 groups: normal control group, Zhengtian Pill (, ZTP) group, Western medicine group, and high-dose (5.2 g/kg), medium-dose (2.6 g/kg) and low-dose (1.3 g/kg) of QTG groups. After completing the prophylactic treatment for 3 days, hot-plate test and acetic acid-induced writhing test were used to assess the analgesic effect, and spontaneous locomotor test and sodium pentobarbital-induced hypnosis activity were adopted to estimate the sedative effect. Sprague-Dawley rats were grouped into normal control group, model group, ZTP group, rizatriptan group, and high-dose (3.6 g/kg), medium-dose (1.8 g/kg), and low-dose (0.9 g/kg) of QTG groups. After gavage for continuous 7 days, rats were intraperitoneally injected nitroglycerin, and 4 h later, blood samples were collected from postcava for measuring the levels of plasma calcitonin gene-related peptide (CGRP) and beta-endorphin (β-EP) by radioimmunoassay. Subsequently, rats were perfused transcardially and the brain tissues containing the trigeminal nucleus caudalis (TNC) were achieved for detecting the number of Fos-immunoreactive cells by immunohistochemical method.

RESULTS

In the mice experiments, compared with the normal control group, high- and medium-dose of QTG groups significantly raised the pain threshold (P<0.01), reduced the number of writhing response (P<0.01) and spontaneous activity (P<0.01), but had no influence on the sleeping rate of mice (P>0.05), and low-dose of QTG group also raised the pain threshold at 120 min (P=0.007), as well as lowered locomotor activity of mice at 2 h (P=0.003). On the study of migraine model rats, high- and medium-dose of QTG groups remarkably down-regulated the levels of plasma CGRP (P<0.01), up-regulated the levels of plasma β-EP (P<0.01) and inhibited the expression of Fos protein in TNC (P<0.01), compared with the model group.

CONCLUSIONS

QTG has obvious analgesic and sedative action and its mechanism on relieving migraine may be through regulating the levels of neurotransmitters and/or neuropeptides, and inhibiting the activation of Fos pathway.

摘要

目的

评价奇龙头痛颗粒（QTG）的镇痛和镇静作用，并探讨其可能的作用机制。

方法

将昆明小鼠随机分为6组：正常对照组、正天丸（ZTP）组、西药组以及QTG高剂量（5.2 g/kg）、中剂量（2.6 g/kg）和低剂量（1.3 g/kg）组。在进行3天的预防性治疗后，采用热板法和醋酸致扭体试验评估镇痛效果，采用自主活动试验和戊巴比妥钠诱导的催眠活动评估镇静效果。将Sprague-Dawley大鼠分为正常对照组、模型组、ZTP组、利扎曲普坦组以及QTG高剂量（3.6 g/kg）、中剂量（1.8 g/kg）和低剂量（0.9 g/kg）组。连续灌胃7天后，大鼠腹腔注射硝酸甘油，4小时后，从下腔静脉采集血样，采用放射免疫分析法测定血浆降钙素基因相关肽（CGRP）和β-内啡肽（β-EP）水平。随后，经心脏灌注大鼠，获取含有三叉神经尾核（TNC）的脑组织，采用免疫组织化学方法检测Fos免疫反应性细胞数量。

结果

在小鼠实验中，与正常对照组相比，QTG高剂量和中剂量组显著提高了痛阈（P<0.01），减少了扭体反应次数（P<0.01）和自主活动（P<0.01），但对小鼠的睡眠率无影响（P>0.05），QTG低剂量组在120分钟时也提高了痛阈（P=0.007），并在2小时时降低了小鼠的运动活性（P=0.003）。在偏头痛模型大鼠研究中，与模型组相比，QTG高剂量和中剂量组显著下调了血浆CGRP水平（P<0.01），上调了血浆β-EP水平（P<0.01），并抑制了TNC中Fos蛋白的表达（P<0.01）。