摘要
目的:基于文献数据挖掘探讨国内外腹泻型肠易激综合征(IBS-D)动物模型的造模要素,为完善其造模方法和评价指标提供参考与建议.方法:通过计算机检索中国知网、万方、维普、中华医学期刊全文数据库、PubMed数据库,获取2014-2024年中有关IBS-D动物实验的相关文献,将实验动物种类、性别、体质量、造模方法、造模周期、干预对照方式、成模标准及检测指标进行整理,应用Microsoft Excel 2021软件建立数据库并进行统计,分析IBS-D动物模型的模型特点.结果:归纳总结符合纳入标准的398篇文献,建立IBS-D动物模型多选用SD大鼠、Wistar大鼠和C57BL/6小鼠,动物性别以雄性居多,通常选用6~8周龄的大鼠,小鼠多集中在4~6周龄.干预对照中,西医以匹维溴铵为主,中药以痛泻要方为主,针灸以电针为主.造模方式中,以多因素联合的复合造模方法为主.造模周期多集中在1~14d和15~30d.造模成功标准主要根据动物表观情况、粪便情况、内脏敏感性、胃肠动力、行为学、病理等方面进行评价.检测指标主要包括表观指标、病理指标、生化指标、氧化应激、脑肠肽、神经递质、炎症因子、免疫功能、肠道通透性、自噬、凋亡、相关信号通路相关蛋白、肠道菌群及其代谢产物等.结论:IBS-D动物模型目前造模方法较多,尚未形成统一公认的造模方法,相同造模方法在不同研究中的操作及模型评价标准尚不统一.基于数据挖掘的结果,笔者认为多因素联合的复合造模方法更能贴近IBS-D病理生理过程,可以较好地模拟IBS-D患者腹痛、腹泻等复杂的临床症状,具有较高的临床吻合度,是相对比较推荐的造模方法.动物模型各方面均较为符合西医学的标准,中医证候的动物模型相对较少,构建符合中西医临床病证结合要求的IBS-D动物模型未来研究方向之一.
Abstract
Objective:Based on literature data mining,this study explores the modeling elements of diarrhea-predominant irritable bowel syndrome(IBS-D)animal models in China and abroad,providing references and suggestions for improving modeling methods and evaluation indicators.Methods:Relevant literature on IBS-D animal experiments from 2014 to 2024 was retrieved through computer searches in databases such as China National Knowledge Infrastructure(CNKI),Wanfang Data,VIP,Chinese Medical Journals Full-text Database,and PubMed.Information on experimental animal species,gender,body weight,modeling methods,modeling periods,intervention controls,modeling standards,and detection indicators was organized.Microsoft Excel 2021 software was used to establish a database and perform statistical analysis to examine the characteristics of IBS-D animal models.Results:A total of 398 articles that met the inclusion criteria were reviewed.The IBS-D animal models were predominantly established using SD rats,Wistar rats,and C57BL/6 mice.Male animals were more commonly used,with rats typically aged 6-8 weeks and mice aged 4-6 weeks.In terms of interventions,piverium bromide was the main Western medicine,Tongxieyaofang was the primary Chinese medicine,and electroacupuncture was the primary acupuncture method.Among the modeling methods,the multi-factor combined composite modeling approach was the most common.Modeling periods were mainly concentrated between 1-14 days and 15-30 days.The success criteria for modeling were mainly evaluated based on the animal's general condition,fecal appearance,visceral sensitivity,gastrointestinal motility,behavior,and pathology.Detection indicators included apparent indexes,pathological markers,biochemical indicators,oxidative stress,brain-gut peptides,neurotransmitters,inflammatory factors,immune function,intestinal permeability,autophagy,apoptosis,proteins related to relevant signaling pathways,intestinal microbiota and its metabolites,etc.Conclusion:There are various methods for establishing IBS-D animal models,but no unified and universally accepted method has been established.The operation of the same modeling methods and the evaluation standards of the models vary across studies.Based on the results of data mining,the authors suggest that the multi-factor combined composite modeling approach most closely reflects the pathophysiological processes of IBS-D,better simulating the complex clinical symptoms of IBS-D patients,such as abdominal pain and diarrhea,and has a high degree of clinical relevance.This method is relatively recommended.While animal models in general align with Western medicine standards,models incorporating traditional Chinese medicine(TCM)syndromes are relatively few.Therefore,one of the future directions for research is to establish IBS-D animal models that meet the combined clinical disease and syndrome requirements of both Western and Chinese medicine.