芎麻汤有效部位防治肝阳上亢兼瘀血型偏头痛的作用机制
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篇名: 芎麻汤有效部位防治肝阳上亢兼瘀血型偏头痛的作用机制
TITLE: The mechanism of effective fractions from Xiongma decoction in the treatment of migraine model rats with hyperactivity of liver-yang and blood stasis
摘要: 目的 探究芎麻汤有效部位防治肝阳上亢兼瘀血型偏头痛的作用机制。方法70只雄性SD大鼠按体质量随机分为正常组、模型组、阳性对照组(盐酸氟桂利嗪胶囊0.9mg/kg)及芎麻汤有效部位低、高剂量组(乙酸乙酯提取物0.87、3.46g/kg,正丁醇提取物1.80、7.20g/kg)。除正常组外,其余各组大鼠灌胃附子汤(2g/kg),每天1次,连续4周,复制肝阳上亢证模型;造模第15天,各给药组同时灌胃相应药物,每天1次,连续2周;造模第29天,电刺激大鼠三叉神经节复制肝阳上亢兼瘀血型偏头痛模型后,按前述方法再维持给药1次。观察大鼠宏观体征及行为表现;取大鼠三叉神经颈髓复合体(TCC),分别采用免疫组织化学法、RT-qPCR法、Westernblot法检测瞬时受体电位香草酸亚型1(TRPV1)、降钙素基因相关肽(CGRP)、降钙素受体样受体(CRLR)、活性修饰蛋白受体1(RAMP1)的阳性表达、mRNA及蛋白相对表达量。结果模型组大鼠出现肝阳上亢兼瘀血型偏头痛相关的宏观体征及行为表现。末次给药30min后,芎麻汤有效部位各组大鼠以上情况均明显改善。与正常组相比,模型组大鼠TCC内TRPV1、CGRP、CRLR、RAMP1阳性表达、mRNA及蛋白相对表达量均显著升高(P<0.05)。与模型组相比,芎麻汤有效部位各组大鼠TCC内上述指标大部分显著降低(P<0.05)。结论芎麻汤防治肝阳上亢兼瘀血型偏头痛的作用机制可能与抑制TCC内TRPV1-CGRP/CGRP受体信号通路的活性有关。
ABSTRACT: OBJECTIVE To expl ore the mechanism of effe ctive fractions from Xiongma decoction in the treatment of migraine with hyperactivity of liver-yang and blood stasis. METHODS Totally 70 male SD rats were randomly divided into normal group , model group ,positive control group (Flunarizine hydrochloride capsules 0.9 mg/kg),low-dose and high-dose groups of Xiongma decoction effective fractions (ethyl acetate extract 0.87,3.46 g/kg,n-butanol extract 1.80,7.20 g/kg). Except for normal group , rats in other groups were given aconite decoction (2 g/kg),once a day ,for 4 consecutive weeks to establish the hyperactivity model of liver-yang. On the 15th day of modeling ,all administration groups were given corresponding drugs intragastrically at the same time ,once a day ,for 2 consecutive weeks. On the 29th day of modeling ,rats trigeminal ganglion was stimulated to establish the migraine model with hyperactivity of liver-yang and blood stasis ,then the medication was maintained for another time according to the above method. The macroscopic signs and behavior of the rats were observed ;positive expression ,mRNA and protein expression of transient receptor potential vanilloid 1 (TRPV1),calcitonin generelated peptide (CGRP),calcitonin receptor-like receptor (CRLR) and receptor-associated membrane proteins 1 (RAMP1) in trigeminal cervical spinal complex (TCC) were detected by immunohistochemistry ,RT-qPCR and Western blot assay. RESULTS Rats in model group showed macrophysical signs and behaviora l manifestations related to migraine with hyperactivity of liver-yang and blood stasis. Thirty minutes after last administration ,the above conditions of rats in Xiongma decoction effective fraction groups were improved significantly. Compared with normal group , positive expression,mRNA and protein expression of TRPV 1,CGRP, CRLR and RAMP 1 in TCC of rats in the model group were significantly increased (P<0.05). Compared with model zengguirong@hnse.org group, most of above indicators in Xiongma decoction effective fraction groups were significantly decreased (P<0.05). CONCLUSIONS The mechanism of Xiongma decoction in preventing and treating migraine with hyperactivity of liver-yang and blood stasis may be related to inhibit the activity of TRPV1-CGRP/CGRP receptor signaling pathway in TCC.
期刊: 2022年第33卷第16期
作者: 刘顶鼎,刘冬,常露露,王静茹,吴雪梅,郭建生,曾贵荣
AUTHORS: LIU Dingding ,LIU Dong,CHANG Lulu,WANG Jingru,WU Xuemei ,GUO Jiansheng ,ZENG Guirong
关键字: 芎麻汤;有效部位;肝阳上亢证;瘀血型偏头痛;瞬时受体电位香草酸亚型1;降钙素基因相关肽
KEYWORDS: Xiongma decoction ;effective fraction ;hyperactivity of liver-yang ;migraine of blood stasis ;transient receptor
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