疏肝健脾中药联合益生菌治疗失眠的临床疗效及对血清5-羟色胺、褪黑素、血管活性肠肽水平的影响

Clinical efficacy of herbal medicine for soothing liver and strengthening spleen combined with probiotics in the treatment of insomnia and its influence on serum levels of 5-hydroxytryptamine,melatonin and vasoactive intestinal peptide

关键词:  疏肝健脾法  益生菌  失眠  5-羟色胺  褪黑素  血管活性肠肽  多导睡眠图

Key words:  soothing liver and invigorating spleen method  probiotics  insomnia  5-hydroxytryptamine(5-HT)  melatonin(MT)  vasoactive intestinal peptide(VIP)  polysomnography(PSG)

摘要:

[目的] 观察疏肝健脾中药联合益生菌治疗失眠（肝郁脾虚型）的临床疗效及对血清5-羟色胺（5-HT）、褪黑素（MT）、血管活性肠肽（VIP）水平的影响。[方法] 选取2021年10月—2022年10月于河北中医药大学第一附属医院睡眠中心门诊就诊的130例中医辨证属于肝郁脾虚型失眠患者作为研究对象，按随机数字表法随机分为观察组65例和对照组65例。对照组给予右佐匹克隆片，2mg/日，睡前口服。观察组给予基于疏肝健脾法拟定的中药免煎颗粒及双歧杆菌乳杆菌三联活菌片，均为2次/日，饭后服用。两组疗程均为4周。观察2组患者治疗前后匹兹堡睡眠质量指数评定量表（PSQI）评分、汉密尔顿抑郁量表（HAMD-17）评分、胃肠道症状量表（GSRS）评分和血清5-HT、MT、VIP水平以及多导睡眠图（PSG）相关参数的变化情况，于停药2周后随访时重复观察患者PSQI、HAMD-17、GSRS评分情况，并评价2组患者的临床疗效和安全性。[结果] 1）PSQI、HAMD-17、GSRS评分：治疗4周后及停药2周随访时，2组患者的PSQI各因子评分、PSQI总分、HAMD-17评分及GSRS评分均低于治疗前（P＜0.05）；观察组PSQI的睡眠时间、睡眠质量、睡眠障碍、日间功能障碍等各因子评分、PSQI总分、HAMD-17评分及GSRS评分的降低程度显著优于对照组（P＜0.05）。2）实验室指标：治疗4周后，2组患者血清5-HT、MT及VIP水平均高于治疗前（P＜0.05）；观察组血清5-HT、MT及VIP水平均显著高于对照组（P＜0.05）。3）PSG监测：治疗4周后，2组患者PSG的总睡眠时间（TST）、睡眠潜伏期（SL）、觉醒时间（AWT）等3项参数值均优于治疗前（P＜0.05）；观察组PSG的TST、AWT参数值的改善程度显著优于对照组（P＜0.05），而SL参数值的改善程度虽低于对照组，但差异无统计学意义（P＞0.05）。4）临床疗效：治疗4周后，观察组的愈显率为70.97%，高于对照组的45.16%（P＜0.05）。5）不良反应发生率：治疗期间，观察组不良反应发生率为4.84%，低于对照组的22.58%（P＜0.05）。[结论] 疏肝健脾中药联合益生菌可有效提高患者的睡眠质量，改善抑郁情绪及胃肠道功能，提升相关神经递质和激素的水平，临床疗效确切，远期疗效显著，且不良反应较少，安全性较高。

Abstract:

[Objective] To observe the clinical efficacy of Shugan Jianpi method combined with probiotics in the treatment of insomnia (liver depression and spleen deficiency type) and the influence of serum 5-hydroxytryptamine (5-HT),melatonin (MT) and vasoactive intestinal peptide(VIP) levels. [Methods] A total of 130 insomnia patients with traditional Chinese medicine syndrome differentiation of liver depression and spleen deficiency treated in the outpatient department of sleep center of the First Affiliated Hospital of Hebei University of Traditional Chinese Medicine from October 2021 to October 2022 were selected as research objects. According to the random number table method,they were divided into the observation group(65 cases) and the control group(65 cases). The control group was given dexzopiclone tablets,2 mg/day,oral before sleep. Observation group was given based on the liver spleen method for traditional Chinese medicine from fried particles and bifidobacterium lactobacillus sanlian living bacterium,are 2 times/day,after meals. The treatment course of both groups was 4 weeks. The changes of pittsburgh sleep quality index (PSQI) score,hamilton depression scale (HAMD-17) score,gastrointestinal symptoms(GSRS) score,serum 5-HT,MT,VIP level and polysomnogram(PSG) related parameters before and after treatment were observed in the 2 groups. PSQI,HAMD-17 and GSRS scores were repeatedly observed at follow-up 2 weeks after drug withdrawal. And the clinical efficacy and safety evaluation of 2 groups of patients. [Results] 1) PSQI,HAMD-17 and GSRS scores:after 4 weeks of treatment and 2 weeks of follow-up after drug withdrawal,PSQI factor scores,PSQI total score,HAMD-17 score and GSRS score of 2 groups were lower than before treatment(P<0.05);the sleep time,sleep quality,sleep disorder,daytime dysfunction and other factors scores of PSQI,PSQI total score,HAMD-17 score and GSRS score of observation group were significantly lower than those of control group(P<0.05).2) Laboratory indicators:after 4 weeks of treatment,serum 5-HT,MT and VIP levels in 2 groups were higher than before treatment(P<0.05);the levels of 5-HT,MT and VIP in the observation group were significantly higher than those in the control group(P<0.05).3) PSG monitoring:after 4 weeks of treatment,the total sleep time(TST),sleep latency(SL) and awakening time(AWT) of PSG in the two groups were better than those before treatment(P<0.05). The improvement degree of TST and AWT parameters of PSG in the observation group was obviously better than that in the control group(P<0.05),while the improvement degree of SL parameters was lower than that in the control group,but there was no statistically significant difference(P>0.05).4) Clinical efficacy:after 4 weeks of treatment,the recovery rate of observation group was 70.97%,which was higher than that of control group 45.16%(P<0.05).5) Incidence of adverse reactions:during treatment,the incidence of adverse reactions in the observation group was 4.84%,lower than that in the control group 22.58%(P<0.05). [Conclusion] Soothing the liver and strengthening the spleen combined with probiotics can effectively improve patients' sleep quality,improve depression and gastrointestinal function,and enhance the levels of related neurotransmitters and hormones. The clinical efficacy is accurate,the long-term efficacy is significant,and fewer adverse reactions,and the safety is high.