理饮汤联合封髓汤治疗脾胃虚寒型慢性咽炎患者的临床效果及其潜在作用机制

Clinical effect of Liyin Decoction combined with Fengsui Decoction for the treatment of patients with chronic pharyngitis in spleen and stomach deficiency with cold manifestation and its potential mechanism

目的 观察理饮汤联合封髓汤治疗脾胃虚寒型慢性咽炎的临床效果,并基于网络药理学方法探讨其潜在的作用机制。方法 (1)将100例脾胃虚寒型慢性咽炎患者随机分为观察组和对照组,各50例。观察组患者服用理饮汤联合封髓汤治疗,对照组患者口服喉咽清口服液治疗,两组均治疗2周。对比两组患者治疗后的临床疗效,以及治疗前后中医证候积分及血清白细胞介素(IL)-6、IL-10、肿瘤坏死因子(TNF)-α水平。(2)利用中药系统药理学数据库及分析平台检索理饮汤和封髓汤的药物活性成分,利用PharmMapper数据库、本草组鉴数据库、UnitProt数据库筛选活性成分的作用靶点。通过GeneCards~?数据库和OMIM~?数据库获取慢性咽炎相关靶点后,将其与活性成分作用靶点取交集。通过STRING数据库构建交集靶点的蛋白-蛋白相互作用网络后,利用Cytoscape 3.9.1软件筛选核心靶点。使用DAVID 6.7数据库对核心靶点进行富集分析。结果 (1)观察组的总有效率高于对照组(P<0.05)。治疗后,两组患者的咽部干痒、刺激性咳嗽和咽黏膜状况的积分较治疗前降低,血清IL-6和TNF-α水平较治疗前降低,血清IL-10水平较治疗前升高,且观察组的上述指标优于对照组(P<0.05)。(2)共获得理饮汤联合封髓汤治疗慢性咽炎的核心靶点34个,包括IL-6、IL-10、TNF等。通路富集分析结果显示,交集靶点主要涉及丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)、TNF等信号通路。功能富集分析结果显示,核心靶点参与信号转导、细胞凋亡过程的负调控、对药物反应等生物过程,富集于细胞核、胞质溶质、核质等细胞组分,涉及蛋白结合、酶结合、转录因子结合等分子功能。结论 理饮汤联合封髓汤治疗脾胃虚寒型慢性咽炎具有较好的临床效果,可以有效改善患者的临床症状,降低血清炎症因子IL-6、TNF-α水平,以及提升IL-10水平。其潜在作用机制可能是药物中多种活性成分通过作用于IL-6、TNF-α、IL-10等核心靶点,参与调节PI3K/AKT、TNF和MAPK等多条炎症相关性信号通路,从而发挥抑制炎症的作用。

Objective To observe the clinical effect of Liyin Decoction combined with Fengsui Decoction for the treatment of chronic pharyngitis in spleen and stomach deficiency with cold manifestation,and to explore its potential mechanism based on network pharmacology method.Methods(1)A total of 100 patients with chronic pharyngitis in spleen and stomach deficiency with cold manifestation were randomly divided into observation group or control group,with 50 cases in each group.Patients in the observation group received Liyin Decoction combined with Fengsui Decoction for treatment,while the control group was orally administrated Houyanqing Oral Liquid for treatment.The two groups were treated for 2 weeks.The post-treatment clinical efficacy,and pre-and post-treatment Traditional Chinese Medicine syndromes scores,serum interleukin(IL)-6 level,IL-10 level,tumor necrosis factor(TNF)-αlevel were compared between the two groups.(2)The active pharmaceutical components of Liyin Decoction and Fengsui Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the effect targets of the active components were screened from the databases of PharmMapper,Guided Database of Traditional Chinese Medicine,and UnitProt.After obtaining targets related to chronic pharyngitis through the databases of GeneCards and OMIM,the intersection between the targets as above and the effect targets of active components was acquired.The protein-protein interaction network of intersection targets was established by the STRING database,after that the core targets were screened by employing the Cytoscape 3.9.1 software.The DAVID 6.7 database was used to perform enrichment analyses on the core targets.Results(1)The total effective rate of the observation group was higher than that of the control group(P<0.05).After treatment,the scores of dry and itchy pharyngeal,irritable cough,pharyngeal mucosa status,and serum IL-6,TNF-αlevels were decreased,whereas serum IL-10 level was elevated of the two groups as compared with before treatment;moreover,the observation group exhibited superior indices as above to compare with the control group(P<0.05).(2)A total of 34 core targets of Liyin Decoction combined with Fengsui Decoction for the treatment of chronic pharyngitis were obtained,including IL-6,IL-10,and TNF,etc.The results of pathway enrichment analysis revealed that the intersection targets were mainly involved in signaling pathways of mitogen activated protein kinase(MAPK),phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT),TNF,etc.The results of functional enrichment analysis interpreted that the core targets participated in biological processes with respect to signal transduction,negative regulation of cell apoptosis process,reaction to medicines,etc.,and were enriched in cellular compositions in terms of nucleus,cytoplasmic solute,nucleoplasm,etc.,and were involved in molecular functions of protein binding,enzyme binding,transcription factor binding,etc.Conclusion Liyin Decoction combined with Fengsui Decoction for the treatment of chronic pharyngitis in spleen and stomach deficiency with cold manifestation exerts a favorable clinical effect,which can effectively ameliorate patients′clinical symptoms,decrease serum inflammatory factors IL-6 and TNF-αlevels,and increase serum IL-10 level.Its potential mechanism may be that multiple active pharmaceutical components can participate in the regulation of PI3K/AKT,TNF,MAPK and other inflammation-related signaling pathways,thereby inhibiting inflammations by acting on the core targets such as IL-6,TNF-α,IL-10.