基于血清外泌体蛋白组复杂网络分析的电针潜在治疗病症预测

Study on potential therapeutic diseases of acupuncture based on proteomics of serum exosome combined with complex network analysis

目的:探索电针潜在治疗病症,为扩大电针临床应用范围提供依据。方法:将24只Wistar大鼠随机分为空白对照组、电针组、佐剂性关节炎组、佐剂性关节炎+电针组,电针14次治疗后提取血清,ExoQuick法提取血清外泌体,Label Free定量蛋白组学技术鉴定并筛选电针血清外泌体显著差异蛋白,将电针显著差异蛋白作为源数据,在人类疾病数据库查找与显著差异蛋白相关的疾病,通过Gephi软件构建正常电针显著差异蛋白-疾病网和模型电针显著差异蛋白-疾病网,找出正常电针显著差异蛋白和模型电针显著差异蛋白二者皆相关的疾病,并联合应用连入度、加权入度、PageRank等运行算法筛选与显著差异蛋白相关度高的疾病,剔除世界卫生组织、美国国立卫生研究院及国内《现代针灸病谱》已推荐的针灸治疗病症,最终确定电针可能的潜在治疗病症。结果:筛选出电针潜在治疗病症100种,其中32种肿瘤、15种免疫系统疾病、15种循环系统疾病、6种传染病、5种泌尿生殖系统疾病、4种代谢性疾病、4种骨骼肌肉系统和结缔组织疾病、3种消化系统疾病、2种皮肤疾病、2种神经系统疾病、1种五官疾病、1种呼吸系统疾病以及10种其他疾病。结论:电针潜在适应病症广泛,涉及多系统疾病,其中免疫系统疾病、肿瘤可能是电针重要的潜在治疗病症。

Objective:To explore the potential therapeutic effect of acupuncture on diseases,and provide a basis for expanding the clinical application of acupuncture.Methods:Twenty-four Wistar rats were randomly divided into blank control group(NC),electroacupuncture group(EA),complete Freund’s adjuvant group(CFA)and CFA+electroacupuncture group(CFA+EA).After 14 times of acupuncture treatment,serum was extracted and ExoQuick method was used to extract serum exosomes Label Free quantitative proteomics technology was used to identify and screen the significant difference proteins of acupuncture serum exosomes.The significant difference proteins of acupuncture were used as the source data to find the diseases related to the significant difference proteins in the human disease database(MALACARD).The normal acupuncture significant difference protein disease network and model acupuncture significant difference protein disease network was constructed by Gephi software to find out the diseases related to the significant difference proteins of both normal acupuncture and model acupuncture,the running algorithms such as connectivity,weighted penetration,and PageRank were combined to screen the diseases with high correlation with significant difference proteins.Eliminating the acupuncture treatment disease that have be recommended by the World Health Organization,the National Institutes of Health of the United States,and the Disease Spectrum of Modern Acupuncture and Moxibustion in China,and finally determine the possible potential therapeutic diseases of acupuncture.Results:A total of 100 kinds of potential therapeutic diseases were screened out,including 32 kinds of tumor,15 kinds of immune system diseases,15 kinds of circulatory system diseases,6 kinds of infectious diseases,5 kinds of urogenital system diseases,4 kinds of metabolic diseases,4 kinds of skeletal muscle system and connective tissue diseases,3 kinds of digestive system diseases,2 kinds of skin diseases,2 kinds of nervous system diseases,1 kind of five sense organ diseases,1 kind of respiratory system diseases,and 10 other diseases.Conclusion:Acupuncture has a wide range of potential diseases,involving multi-system diseases,among which immune system diseases and tumors may be important potential therapeutic diseases.