新型冠状病毒感染恢复期合并高血压病中医证候特征分析及机制探索

TCM Syndrome Characteristics Analysis and Mechanism Exploration of COVID-19 in the Recovery Period Combined with Hypertension

目的探讨新型冠状病毒感染(corona virus disease 2019,COVID-19)恢复期合并高血压病患者的中医证候特征及分子通路机制。方法按照临床流行病学方法收集武汉11家医院的1314例COVID-19患者的临床资料,建立“新型冠状病毒感染病例登记系统”(http://covid-19.keyanyun.com),选取120例COVID-19恢复期合并高血压病患者的临床资料作为研究对象并进行长期随访,收集其出院后的中医四诊资料,通过真实世界研究(realworld study,RWS)方法进行双向队列研究,采用频数统计、因子分析、聚类分析等统计学方法,统计其主要症状、病位、病性及中医证型分布。结合前方得出的各证型中医证候特征,以“症状”为切入点,利用生物信息学方法,获得本研究疾病靶点及各证型中医证候表型靶点,进行京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果中医症状以喘促气短、乏力、胸闷、健忘、失眠、咽干口渴、自汗、咳嗽、咳痰、神疲、痰白、口苦为主,舌象以苔白、舌胖大、苔黄为主,脉象以脉细、脉沉多见。因子分析共提取8个公因子,病位证素主要为肺、脾、肝、肾、心,病性证素主要是气虚、阴虚、湿、热。聚类分析表明中医证型以肺脾气虚证、气阴两虚证、肝火犯肺证、肺肾气虚证为主。4个证型的目标靶点数目分别为202、201、155、212,KEGG通路富集结果表明对应通路大致相似,但各证型的信号通路侧重点不同。除肺肾气虚证外,其余3个证型都对Toll样受体信号通路、IL-17信号通路、TNF信号通路等具有较强干预作用。结论COVID-19恢复期合并高血压病的中医证候分散性良好,中医证型以肺脾气虚证、气阴两虚证、肝火犯肺证、肺肾气虚证为主,病机表现为邪气未尽、正气未复,信号通路主要与病毒感染、免疫炎症相关,可为临床辨证用药提供中医学及分子生物学借鉴。

Objective To explore the characteristics of TCM syndromes and molecular pathway mechanisms of patients with hypertension during the recovery period of corona virus disease 2019(COVID-19).Methods According to the clinical epidemiological method,the clinical data of 1314 COVID-19 patients from 11 hospitals in Wuhan were collected,and the“Coronavirus Disease 2019 Case Registration System”(http://covid-19.keyanyun.com)was established.The clinical data of 120 patients with COVID-19 convalescence and hypertension were selected as the research object and followed up for longterm follow-up.The four-diagnosis data of traditional Chinese medicine was collected after discharge,and the real-world study(RWS)method was used to conduct the two-way cohort study,and statistical methods such as frequency statistics,factor analysis,and cluster analysis were used to calculate the distribution of its main symptoms,disease locations,disease properties,and TCM syndrome types.Combining the features of TCM syndromes of various syndrome types obtained in the front,using“symptoms”as the breakthroughpoint,using bioinformatics methods,to obtain the disease targets of this study and the phenotype targets of TCM syndromes of various syndrome types,and carry out Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Results TCM symptoms are mainly shortness of breath,fatigue,chest tightness,forgetfulness,insomnia,dry throat and thirst,spontaneous sweating,coughing,sputum,fatigue,white phlegm,and bitter taste in mouth.The tongue picture is mainly white,fat and yellow,and the pulse is often thin and heavy.A total of 8 common factors were extracted by factor analysis.The disease location syndromes are mainly lung,spleen,liver,kidney,and heart.And the disease syndromes are mainly Qi deficiency,Yin deficiency,dampness and heat.Cluster analysis showed that the main types of TCM syndromes were deficiency of lung and spleen Qi type,deficiency of both Qi and Yin type,liver fire invading the lung type,and deficiency of lung and kidney Qi type.The target numbers of the four syndrome types are 202,201,155,and 212 respectively.The enrichment results of KEGG pathway show that the corresponding pathways are roughly similar,but the signal pathways of each syndrome type have different emphasis.Except for the syndrome of deficiency of lung and kidney Qi,the other three syndrome types have a strong intervention effect on Toll-like receptor signaling pathway,IL-17 signaling pathway,TNF signaling pathway and other pathways.Conclusion The TCM syndromes of COVID-19 during the recovery period combined with hypertension are well dispersed.The TCM syndromes are mainly deficiency of lung and spleen Qi type,deficiency of both Qi and Yin type,liver fire invading the lung type,and deficiency of lung and kidney Qi type.The pathogenesis is manifested as the pathogenic Qi is not exhausted,the vital Qi is not restored.The signal pathway is mainly related to viral infection and immune inflammation,which can provide reference for clinical syndrome differentiation related to Chinese medicine and molecular biology.