刘顶鼎 杨菁 刘冬 郭建生 毛效贤 曾贵荣 周英

摘 要 目的：研究芎麻湯提取物对肝阳上亢兼瘀血型偏头痛模型大鼠脑组织中5-羟色胺（5-HT）、降钙素基因相关肽（CGRP） 的影响。方法：将50只雄性自发性高血压（SHR）大鼠按血压随机分为模型对照组、正天丸阳性对照组（1.6 g/kg）和芎麻汤提取物低、中、高剂量组（4.5、9.0、18.0 g/kg，以生药量计），每组10只;并另取10只正常大鼠作为正常对照组。给药组大鼠分别灌胃相应药物，每天1次，连续28 d;正常对照组和模型对照组大鼠灌胃等体积生理盐水。末次给药后，除正常对照组外，其余各组大鼠均采用电刺激三叉神经节（10 min）法复制肝阳上亢兼瘀血型偏头痛大鼠模型，并于造模后再维持给药1次。30 min后，观察大鼠一般行为学及舌质情况，测定大鼠血压，采用酶联免疫吸附法测定大鼠脑组织中5-HT、CGRP含量，并采用Western blot法测定大鼠脑组织中CGRP蛋白表达水平。结果：与正常对照组比较，模型对照组大鼠出现眼结膜颜色加深变红、过度理毛、甩头等行为学变化，大部分大鼠舌质紫暗，并且其收缩压和脑组织中CGRP含量及蛋白表达水平均明显升高（P<0.05或P<0.01），脑组织中5-HT含量显著降低（P<0.01）。与模型对照组比较，各给药组大鼠的上述行为学变化及舌质变化均明显改善;正天丸阳性对照组和芎麻汤提取物高剂量组大鼠收缩压、脑组织中CGRP含量及蛋白表达水平显著降低（P<0.05）;正天丸阳性对照组和芎麻汤提取物中、高剂量组大鼠脑组织中5-HT含量显著升高（P<0.05）。结论：芎麻汤提取物对肝阳上亢兼瘀血型偏头痛模型大鼠有明显的保护作用，其机制可能与降低脑组织中CGRP含量、升高脑组织中5-HT含量有关。

关键词 芎麻汤提取物;肝阳上亢兼瘀血型偏头痛模型;自发性高血压大鼠;5-羟色胺;降钙素基因相关肽

中图分类号 R285 文献标志码 A 文章编号 1001-0408（2020）01-0024-06

DOI 10.6039/j.issn.1001-0408.2020.01.05

ABSTRACT   OBJECTIVE： To study the effects of the extract of Xiongmatang on 5-HT and CGRP in brain tissue of rats with liver-yang hyperactivity and blood stagnation migraine. METHODS： Fifty male spontaneously hypertension （SHR） rats were randomly divided into model control group， Zhengtian pill positive control group （1.6 g/kg）， the extract of Xiongmatang low-dose， medium-dose and high-dose groups （4.5， 9.0， 18.0 g/kg， by crude drug）， with 10 rats in each group. Another 10 normal rats were taken as normal control group. Administration group was given relevant medicine intragastrically， once a day， for consecutive 28 d. Normal control group and model control group were given equal volume normal saline intragastrically. After last administration， except for normal control group， other groups were used to stimulate trigeminal ganglia （10 min） to establish liver-yang hyperactivity and blood stagnation migraine model， and maintained the administration once more after making the model. 30 min later， general behavior and tongue quality of rats were observed， and the blood pressure was measured; the contents of 5-HT and CGRP in cerebral tissue of rats were determined by ELISA. The protein expression of CGRP in cerebral tissue of rats were determined by Western blot method. RESULTS： Compared with the normal control group， the rats in the model control group had behavioral symptoms， such as the color of conjunctiva deepened and reddened， excessive hairdressing， head flicking， and most of the rats had purple tongue; the systolic pressure and the content and protein expression of CGRP were all increased obviously （P<0.05 or P<0.01）， while the content of 5-HT in cerebral tissue was decreased obviously （P<0.01）. Compared with model control group， general behavior and tongue quality of rats were improved significantly in administration groups. Systolic pressure， the content and the protein expression of CGRP in cerebral tissue of rats were decreased significantly in Zhengtian pill positive control group and the extract of Xiongmatang high-dose group （P<0.05）， while the content of 5-HT  in cerebral tissue of rats were increased significantly in Zhengtian pill positive control group， the extract of Xiongmatang medium-dose and high-dose groups （P<0.05）. CONCLUSIONS： The extract of Xiongmatang has obvious protective effect on liver-yang hyperactivity and blood stagnation migraine model rats， the mechanism of which may be associated with reducing the content of  CGRP in cerebral tissue and raising the content of 5-HT in cerebral tissue.

KEYWORDS   Extract of Xiongmatang; Liver-yang hyperactivity and blood stagnation migraine model; Spontaneously hypertension rats; 5-HT; CGRP

偏头痛是一种临床常见的神经性疾病，其特征是由神经血管功能障碍引起的周期性头痛。2017年《Lancet》杂志发表的世界卫生组织（WHO）2015年全球疾病负担调查的研究结果表明，偏头痛为人类第六位常见疾病，按失能所致生命损失（Years of life lost to disability，YLDs）计算，偏头痛为第二位致残性疾病[1]。……