芪龙头痛颗粒镇静作用及其抗偏头痛机制研究

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目的研究芪龙头痛颗粒(Qilong Toutong granule,QLTT)的镇静作用、活血化瘀功效及其抗偏头痛机制。方法实验动物随机分为6组:即正常对照组,正天丸组,模型组及QLTT高、中、低剂量组。72只昆明小鼠灌胃给药3 d后,用自主活动实验和协同催眠实验观察QLTT的镇静催眠作用。60只SD大鼠灌胃给药7 d后,皮下注射盐酸肾上腺素注射液2次,期间冰水浸泡5 min复制急性血瘀模型,禁食12 h后取血检测血黏度。60只昆明小鼠经利血平皮下注射9 d复制低5-羟色胺(5-HT)偏头痛模型,从模型复制第3天起,给予相应药物进行灌胃,末次灌胃1 h后,取血与脑组织进行凝血时间和单胺类递质的测定。结果 QLTT高、中、低剂量组与正天丸组自主活动次数减少,提示具有明显的镇静作用(P<0.05,P<0.01),但无催眠作用;可显著改善血瘀模型鼠的血液黏度(P<0.01);增加脑组织5-HT、多巴胺(DA)和去甲肾上腺素(NE)的含量(P<0.05,P<0.01);QLTT高、中剂量组和正天丸组能显著延长低5-HT偏头痛模型小鼠的凝血时间(P<0.01);QLTT中剂量组和正天丸组可提高血浆5-HT水平(P<0.05)。结论 QLTT具有明显的镇静作用和活血化瘀功效,可能是通过提高血浆和脑组织的5-HT、NE和DA的含量,抑制三叉颈复合体神经元的活化,从而减轻偏头痛的疼痛程度。 Objective To study the sedative effect of Qilong Toutong granule (QLTT), its efficacy in promoting blood circulation, and its anti-migraine mechanism. Methods Experimental animals were randomly divided into 6 groups: normal control group, Zhengtian Pill group, model group and QLTT high, middle and low dose groups. The sedative and hypnotic effects of QLTT were observed in 72 Kunming mice after intragastric administration for 3 days, using autonomic activity test and synergy hypnosis experiment. Sixty SD rats were intragastrically administered for 7 days. Subcutaneous injection of epinephrine hydrochloride injection was performed twice. During the period of ice immersion for 5 minutes, the acute blood stasis model was established. The blood viscosity was measured after fasting for 12 hours. 60 Kunming mice were injected subcutaneously with reserpine for 9 days to replicate the hypoxamine (5-HT) migraine model. From the 3rd day after the model was replicated, the corresponding drug was given for gavage. After the last gavage for 1 h, the mice were taken. Blood and brain tissue were assayed for coagulation time and monoamine transmitters. Results The number of locomotor activities in QLTT high, middle and low dose groups and Zhengtian Pills decreased, suggesting significant sedative effect (P<0.05, P<0.01) but no hypnotic effect; it can significantly improve the blood viscosity of blood stasis model rats. (P<0.01); Increased 5-HT, DA, and NE levels in brain tissue (P<0.05, P<0.01); QLTT high, medium dose, and Zhengtian Pills were significantly prolonged. The clotting time was lower in the 5-HT migraine model mice (P<0.01); the plasma 5-HT levels in the QLTT middle-dose group and the Zhengtian Pill group were increased (P<0.05). Conclusion QLTT has obvious sedative effect and blood circulation efficacy, which may be through the increase of 5-HT, NE and DA levels in plasma and brain tissue, inhibiting the activation of trigeminal complex neurons, thereby reducing migraine pain.
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