调中化痰安神合剂镇静催眠作用的药效学研究

An Experimental Study on Pharmacodynamics and Mechanism of Sedative-hypnotic Effect of Tiaozhong Huatan Anshen Mixture

目的探讨调中化痰安神合剂镇静催眠的作用机制。方法健康昆明种小鼠200只,随机分为4组各50只,各组又随机分为空白组、对照组和调中化痰安神合剂高、中、低剂量组(中药高、中、低剂量组),每组10只,分别予生理盐水、艾司唑仑和高、中、低剂量调中化痰安神合剂灌胃给药,每日1次。第1组连续给药7 d,观察各组小鼠给药前后自发活动的次数。第2组连续给药7 d,给药结束60 min后,各组小鼠予戊巴比妥钠30 mg/kg体质量(引起100%小鼠睡眠的最小阈剂量)腹腔注射,记录各组小鼠的睡眠时间。第3组连续给药7 d,给药结束60 min后,各组小鼠予戊巴比妥钠15 mg/kg体质量(引起90%~100%小鼠翻正反射不消失的最大剂量)腹腔注射,观察并记录入睡动物数,计算入睡率。第4组连续给药15 d后脱颈处死,迅速取出脑组织,分批取出匀浆,荧光分光光度法测定小鼠脑组织中5-羟色胺(5-HT)、5-羟吲哚乙酸(5-HIAA)含量。结果与空白组比较,各给药组小鼠活动次数减少、睡眠潜伏期缩短、睡眠持续时间延长、入睡率提高(P<0.01,P<0.05),其中对照组和中药高剂量组镇静效果明显优于其他给药组,差异有统计学意义(P<0.05),但2组比较差异未见统计学意义(P>0.05)。与空白组比较,各给药组小鼠脑内5-HT、5-HIAA含量增加,差异有统计学意义(P<0.01,P<0.05),中药高剂量组增加最显著(P<0.05)。结论调中化痰安神合剂有明显镇静催眠作用,其作用机制可能与增加脑内5-HT合成与代谢有关。

Objective To explore the mechanism of Tiaozhong Huatan Anshen Mixture （THAM）. Methods A total of 200 healthy Kunming mice were randomly and equally divided into first, second, third and fourth major groups. Each major group was further equally divided into blank group, control group and high, medium, low dose THAM groups. Each group was given an equal volume of NS, estazolam, or high, medium, or low dose THAM by gavage for 7 d. For the first major group, the changes in number of spontaneous activities after administration were evaluated. For the second major group, 60 min after administration, each group was given pentobarbital sodium （30 mg/kg body weight, minimum dose for all mice sleeping） by intraperitoneal injection, and the sleep time was recorded. For the third major group, 60 min after administration, each group was given pentobarbital sodium （15 mg/kg body weight, maximum dose for 90%-100% of all mice having righting reflex） by intraperitoneal injection. The number of mice falling asleep was recorded, and the sleep rate was calculated. For the fourth major group, mice were sacrificed after continuous administration 15 d. They were quickly removed brain tissue; homogenates were taken out in batches; 5-HT and 5-HIAA levels in brain tissues were determined according to fluorescence spectrophotometric. Results Compared with the blank group, all treated groups had a reduced number of spontaneous activities, a shortened sleep latency, a prolonged sleep time, and an increased sleep rate after administration （P^0.01, P〈0.05）, with the most significant changesseen in the control group and high-dose THAM group （P^0.05）, with out statistical significance between the two groups （P〉0.05）. Compared with the blank group, brain 5-HT and 5-HIAA levels in all treated groups increased in mice （P 〈0.01, P 〈 0.05）, with the most significant changes seen in the high-dose THAM group （P〈0.05）. Conclusion THAM has a significant sedative-hypnotic effect. The mechanism may be related to increasing brain 5-HT synthesis and metabolism.