南方医科大学学报

南方医科大学学报 ›› 2024, Vol. 44 ›› Issue (2): 217-225.doi: 10.12122/j.issn.1673-4254.2024.02.03

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健脾温阳凝胶剂脐疗治疗脾胃虚弱型慢性腹泻的疗效及机制：一项临床随机对照试验

崔艺馨，王德财，谢东晴，王海明，徐睿鑫，唐潇然，张 印   

  1. 中国人民解放军总医院第六医学中心中医医学部，第一医学中心超声科，北京 100853；航天中心医院，北京 100049
  • 发布日期:2024-03-13

Efficacy of navel application of Jianpiwenyang Gel for chronic diarrhea of spleen and stomach weakness type: a randomized controlled trial and analysis of the mechanism

CUI Yixin, WANG Decai, XIE Dongqing, WANG Haiming, XU Ruixin, TANG Xiaoran, ZHANG Yin   

  1. Department of Traditional Chinese Medicine of the Sixth Clinical Center, Department of Ultrasound of the First Clinical Center, Chinese PLA General Hospital, Beijing 100853, China; Second Outpatient Department, Aerospace Center Hospital, Beijing 100049, China
  • Published:2024-03-13

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摘要： 目的 探讨健脾温阳凝胶剂（SSWYG）治疗慢性腹泻的临床疗效及作用机制。方法 80例脾胃虚弱型慢性腹泻患者随机分为对照组和试验组，每组40例。两组均调整规范的生活方式，对照组给予双歧三联活菌胶囊、试验组给予SSWYG脐疗，1周后评估慢性腹泻的情况。依托中药系统药理学分析平台（TCMSP）、GeneCards、NCBI、OMIM 数据库及 GEO 数据库（GSE14841）获得SSWYG的活性成分和靶点蛋白以及慢性腹泻相关疾病靶点，构建蛋白互作网络（PPI）后，应用拓扑分析获得关键靶点，并对关键靶标进行基因本体（GO）功能富集分析、京都基因与基因组百科全书（KEGG）通路富集分析，运用AutoDock软件进行分子对接以验证 SSWYG 对特定靶标的亲和力及结合特性。结果 对照组和试验组患者胃肠道症状评定量表（GSRS），Bristol评分及中医证候评分均有改善（P<0.05），试验组均优于对照组（P<0.05）；经筛选，SSWYG治疗慢性腹泻的靶点共68个，拓扑分析筛得最可能的关键靶点33个，GO及KEGG富集分析预测出与慢性腹泻相关的TNF、IL-17等多条通路；分子对接研究提示SSWYG的核心成分均与CASP3、JUN、IL6、AKT1、VEGFA关键靶点有较好的亲和力，尤其JUN和CASP3与复方中多种主要活性成分结合能最低、结合最稳定。结论 SSWYG不仅明显改善腹痛、便溏等慢性腹泻的临床症状，还能缓解脘腹痞满、倦怠乏力、神疲懒言等症状，从多个维度提高患者生存质量，其作用机制可能主要通过CASP3、JUN调控TNF、IL-17等信号通路发挥治疗慢性腹泻的药理效应，具有多成分、多靶点、多通路协同调节的特点。

关键词: 健脾温阳凝胶剂；慢性腹泻；脐疗；网络药理学；分子对接

Abstract: Objective To investigate the efficacy of Jianpiwenyang Gel (SSWYG) for treating chronic diarrhea and explore its therapeutic mechanism. Methods Eighty patients with chronic diarrhea of spleen and stomach weakness type were randomized into two groups for interventions with lifestyle adjustment and treatment with bifid triple viable capsules (control group, n=40) or naval application with SSWYG (treatment group, n=40) for one week, after which symptoms of chronic diarrhea were evaluated. The Chinese medicine system pharmacology analysis platform (TCMSP), GeneCards, NCBI, OMIM database and GEO database (GSE14841) were used to obtain the active ingredients and target proteins of SSWYG and chronic diarrhea-related targets. The key targets were obtained by topological analysis for Gene Ontology (GO) and KEGG analyses. The affinity and binding characteristics of SSWYG for specific targets were verified by molecular docking using AutoDock software. Results In both groups, gastrointestinal symptom rating scale (GSRS), Bristol Scale and TCM syndrome scores significantly improved after the treatments (P<0.05), and better effects were observed in the treatment group (P<0.05). Sixty-eight targets of SSWYG in treating chronic diarrhea were obtained, and 33 most probable ones were screened out by topological analysis. GO and KEGG analyses identified several chronic diarrhea-related pathways including the TNF and IL-17 pathways. Molecular docking study showed good affinity of the core components of SSWYG for the key targets CASP3, JNK, IL1B, IL6, and AKT1. JUN and CASP3 had the lowest binding energy and the highest stable binding energy with multiple major active ingredients of SSWYG. Conclusion SSWYG can significantly improve clinical symptoms of chronic diarrhea possibly by regulating the TNF and IL-17 as well as other pathways via CASP3 and JUN, suggesting a complex therapeutic mechanism of SSWYG involving multiple ingredients and targets and coordinated regulation of multiple pathways.

Key words: Jianpiwenyang Gel; chronic diarrhea; navel therapy; network pharmacology; molecular docking