二仙合桂枝汤加味干预绝经综合征潮热症状的疗效及其对肠道菌群结构的影响研究

Study on the Therapeutic Effect of Flavored Erxian and Guizhi Decoction on Hot Flashes in Menopausal Syndrome and Its Effect to Intestinal Flora Structure

目的观察二仙合桂枝汤加味治疗绝经综合征潮热症状的临床疗效,并探讨其改善绝经综合征潮热症状与肠道菌群结构的相关性。方法选取2020年6月-2021年8月就诊于广州中医药大学第一附属医院的绝经综合征患者72例,采用区组化随机方法分为治疗组(36例)和对照组(36例)。治疗组给予二仙合桂枝汤加味治疗,对照组予克龄蒙治疗,连续用药21 d为1个疗程,共3个疗程。比较两组患者治疗前后潮热症状得分、潮热程度、有效率及卵泡刺激素(FSH)、雌二醇(E2)水平。于治疗前后分别取治疗组患者粪便样本进行16S rRNA测序分析,比较治疗前后肠道菌群结构的差异。结果治疗组总有效率为86.2%,对照组为93.5%,两组比较差异无统计学意义(χ2=0.897,P>0.05)。治疗组和对照组均能改善潮热症状评分(P<0.05);对照组可明显降低FSH水平及提高E2水平(P<0.05),而治疗组作用不明显(P>0.05)。治疗组不良事件发生率为11.1%(4/36),低于对照组的30.6%(11/36)(P<0.05)。肠道菌群结构分析结果显示,属水平的Eggerthella(r=-0.426,P=0.002)、Holdemania(r=-0.283,P=0.042)、Erysipelotrichaceae_Clostridium(r=-0.365,P=0.008)与绝经综合征潮热评分呈显著负相关,且二仙合桂枝汤治疗后可上调上述菌群丰度(P<0.05)。结论二仙合桂枝汤加味能有效改善绝经综合征,减轻潮热程度,且不良反应较少。属水平的Eggerthella、Holdemania、Erysipelotrichaceae_Clostridium等肠道菌群可能与潮热的发生有关,二仙合桂枝汤加味可能通过调整肠道菌群结构来改善绝经综合征潮热症状。

Objective To observe the clinical efficacy of flavored Erxian and Guizhi Decoction in the treatment of hot flashes in menopausal syndrome,as well as to analyze and explore the correlation between the structure of intestinal flora and traditional Chinese medicine(TCM)on improving hot flashes in menopausal syndrome.Methods Seventy two patients with menopausal syndrome treated in The First Affiliated Hospital of Guangzhou University of Chinese Medicine from June 2020 to August 2021 were randomly divided into the treatment group(n=36)and the positive control group(n=36).The treatment group was treated with flavored Erxian and Guizhi Decoction,and the positive control group was treated with Climen.The treatment in both groups lasted 3 carses of treatment and 21 consecutive days as one course of treatment.The symptom score of hot flashes,degree of hot flashes,effective rate,follicle stimulating hormone(FSH)and estradiol(E2)of the patients were compared between the two groups before and after treatment.16S rRNA sequencing was performed on fecal samples of patients with hot flashes of menopausal syndrome treated with TCM before and after treatment,and the community structural differences of intestinal flora between the two groups were compared.Results The total effective rate of the treatment group was 86.2%,which was equivalent to 93.5%of the control group(χ2=0.897,P>0.05).Both the treatment group and the control group could improve the score of hot flashes(P<0.05).The level of FSH was significantly reduced and the level of E2 was significantly increased in the positive control group(P<0.05),while the treatment group had no significant effect in this regard(P>0.05).The total incidence of adverse events in the treatment group was lower than that in the control group(P<0.05).In the analysis of intestinal flora community structure,Eggerthella(r=-0.426,P=0.002),Holdemania(r=-0.283,P=0.042)and Erysipelotrichaceae_Clostridium(r=-0.365,P=0.008)were significantly negatively correlated with the score of hot flashes in postmenopausal syndrome,and TCM treatment could upregulate the abundance of the above flora(P<0.05).Conclusion Flavored Erxian and Guizhi Decoction can effectively improve menopausal syndrome and reduce the degree of hot flashes with less adverse reactions.Genus levels of Eggerthella,Holdemania and Erysipelotrichaceae_Clostridium in intestinal flora may be related to the occurrence and development of hot flashes.Flavored Erxian and Guizhi Decoction may improve the symptoms of hot flashes in menopausal patients by adjusting the community structure of intestinal flora.