【目的】探讨加味温胆汤通过抑制超级化激活环核苷酸门控通道 （HCN） 参与抗卒中后抑郁的作用效果。 【方法】将300例肝郁痰阻型卒中后抑郁患者随机分为对照组和观察组，每组各150例。2组患者均接受脑卒中常规基础治疗 （包括抗凝、控制血糖、控制血脂、控制血压等） ，在此基础上，对照组给予黛力新治疗，观察组给予黛力新联合加味温胆汤治疗，疗程为4周。观察2组患者临床疗效及治疗前后汉密尔顿抑郁量表 （HAMD） 评分、抑郁自评量表 （SDS） 评分、改良Barthel指数评分和血清单胺类神经递质水平[神经肽、脑源性神经营养因子 （BDNF） 、5-羟色胺、P物质、神经元特异性烯醇化酶 （NSE） 、视黄醇结合蛋白4 （RBP4） ]以及外周血HCN1、HCN2亚型mRNA表达水平的变化情况，分析外周血HCN1、HCN2亚型mRNA表达水平与HAMD评分、SDS评分的相关性。 【结果】（1） 疗效方面，治疗4周后，观察组的总有效率为92.00% （138/150） ，对照组为80.00% （120/150） ，组间比较，观察组的总有效率 （χ2检验） 和总体疗效 （秩和检验） 均明显优于对照组 （P＜0.01） 。 （2） 量表评分方面，治疗后，2组患者的改良Barthel指数评分均较治疗前明显升高 （P＜0.05） ，HAMD评分和SDS评分均较治疗前明显降低 （P＜0.05） ，且观察组对改良Barthel指数评分的升高幅度及对HAMD评分和SDS评分的降低幅度均明显优于对照组（P＜0.01） 。 （3） 血清单胺类神经递质水平方面，治疗后，2组患者的血清BDNF、神经肽、5-羟色胺水平均较治疗前明显升高（P＜0.05） ，血清NSE、P物质、RBP4水平均较治疗前明显降低 （P＜0.05） ，且观察组对血清BDNF、神经肽、5-羟色胺水平的升高幅度及对血清NSE、P物质、RBP4水平降低幅度均明显优于对照组 （P＜0.05） 。 （4） 外周血HCN1、HCN2亚型mRNA表达水平方面，治疗后，2组患者的HCN1、HCN2亚型mRNA表达水平均较治疗前明显降低 （P＜0.01） ，且观察组对HCN1、HCN2亚型mRNA表达水平的降低幅度均明显优于对照组 （P＜0.05） 。 （5） 相关性分析方面，外周血HCN1、HCN2亚型mRNA表达水平与SDS评分和HAMD评分均呈正相关 （P＜0.001） 。 【结论】在西医常规治疗基础上联合加味温胆汤治疗肝郁痰阻型卒中后抑郁患者的临床疗效良好，可有效减轻患者抑郁程度，改善血清单胺类神经递质水平，提高患者日常生活能力，其抗抑郁机制可能与抑制HCN离子通道有关。

Objective To investigate the outcomes of Jiawei Wendan Decoction participating in post-stroke depression treatment through inhibiting the hyperpolarization-activated cyclic nucleotide-gated channel （HCN） . Methods A total of 300 patients with post-stroke depression of liver depression and phlegm obstruction type were randomly divided into the control group and the observation group，with 150 patients in each group. The two groups were treated with the conventional basic treatment for stroke， including anticoagulants and medicines for controlling blood glucose，lipids and blood pressure. In addition，the control group was given Deanxit orally and the observation group was given Deanxit combined with Jiawei Wendan Decoction orally. The course of treatment for the two groups covered four weeks. After treatment，the clinical efficacy of the patients in the two groups was evaluated. Before and after treatment，the two groups were observed in the changes of Hamilton Depression Scale （HAMD） scores，Self-Rating Depression Scale （SDS） scores，modified Barthel Index scores，and the serum levels of monoamine neurotransmitters of neuropeptide， brain-derived neurotrophic factor （BDNF）， 5-hydroxytryptamine，substance P，neuron-specific enolase （NSE） ，and retinol-binding protein 4 （RBP4） ，and mRNA expression levels of HCN1 and HCN2 subtypes in peripheral blood. Moreover，the correlation between peripheral blood mRNA expression levels of HCN1 and HCN2 subtypes and HAMD scores and SDS scores were analyzed. Results （1）After four weeks of treatment，the total effective rate of the observation group was 92.00% （138/150） ，and that of the control group was 80.00% （120/150） ；the intergroup comparison showed that the total effective rate （tested by chi-square test） and the overall efficacy （tested by rank sum test） of the observation group were significantly superior to those of the control group （P＜0.01） . （2） After treatment，the modified Barthel index scores in the two groups were significantly increased（P＜0.05） and the scores of HAMD and SDS were significantly decreased when compared with those before treatment（P＜0.05），the increase of modified Barthel Index scores as well as the decrease of scores of HAMD and SDS in the observation group was superior to that in the control group（P＜0.01） . （3）After treatment， the serum levels of monoamine neurotransmitters of BDNF，neuropeptide，and 5-hydroxytryptamine in the two groups were significantly increased （P＜0.05） ，and the serum levels of NSE，substance P，and RBP4 were significantly decreased when compared with those before treatment （P＜0.05）；the increase of serum levels of BDNF，neuropeptide，and 5-hydroxytryptamine as well as the decrease of the serum levels of NSE，substance P，and RBP4 in the observation group was superior to that in the control group （P＜0.05） . （4） After treatment，the mRNA expression levels of HCN1 and HCN2 subtypes in the two groups were significantly decreased when compared with those before treatment （P＜0.01） ，and the decrease of the mRNA expression levels of HCN1 and HCN2 subtypes in the observation group was significantly superior to that of the control group （P＜0.05） . （5） The correlation analysis showed that the mRNA expression levels of HCN1 and HCN2 subtypes in the peripheral blood were positively correlated with both SDS scores and HAMD scores （P＜0.001） . Conclusion Jiawei Wendan Decoction combined with conventional western medicine has achieved satisfactory efficacy for the treatment of patients with post-stroke depression of liver depression and phlegm obstruction type，which can effectively reduce the degree of depression，improve the serum levels of monoamine neurotransmitters，and improve the activities of daily living，and its anti-depression mechanism may be related to the inhibition of HCN ion channels.

R277.7

国家自然科学基金项目 （编号：82073824）