基于中西医病证特点的肝郁脾虚型腹泻型肠易激综合征大鼠模型的建立与评价  

Establishment and evaluation of an irritable bowel syndrome with diarrhoea rat model with liver depression and spleen deficiency based on the characteristics of traditional Chinese medicine and Western medicine

作　　者：王晓鸽 李泽伦 康丽杰 崔凯歌 马世博 许二平[2] WANG Xiaoge;LI Zelun;KANG Lijie;CUI Kaige;MA Shibo;XU Erping(Department of Gastroenterology,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou,450000,China;Henan University of Chinese Medicine;Henan Province Hospital of Traditional Chinese Medicine)

机构地区：[1]河南中医药大学第一附属医院脾胃肝胆病科,郑州450000 [2]河南中医药大学 [3]河南中医药大学第二附属医院

出　　处：《中国中西医结合消化杂志》2025年第2期106-111,116,共7页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：国家自然科学基金项目(No:82104776)。

摘　　要：目的:通过新生母子分离-慢性不可预知性多重应激(chronic unpredietable mild stress,CUMS)-三硝基苯磺酸(trinitro-benzene-sulfonic acid,TNBS)三因素叠加建立基于中西医病证特点的肝郁脾虚型腹泻型肠易激综合征(irritable bowel syndrome with diarrhoea,IBS-D)大鼠模型。方法:选用SPF级SD孕鼠生产的雄性子鼠,随机分成正常组和模型组,其中正常组8只,模型组10只。模型组子鼠从出生后的第2~14天,每天固定时间与母鼠进行3 h的分离,分离结束后仍在一起喂养;正常组不予任何干预,第22天断奶,第30天进行随机分笼,母子分离法于第6周末造模结束。TNBS灌肠造模从第7周第1天开始,第9周进行为期21 d的CUMS,第11周造模全部完成(正常组不干预)。造模完成后以CUMS为时间截点,通过对CUMS前后旷场试验、蔗糖水偏嗜试验的测定来评价肝郁证候,通过腹壁回撤反射(abdominal withdrawal reflex,AWR)的测定来评价内脏敏感性,通过粪便含水量的测定来评价腹泻程度,通过体重变化来评价脾虚证候。结果:(1)体重及一般情况:母子分离造模结束时,模型组体重与正常组相比明显降低(P<0.05),而第7周(TNBS造模前),正常组和模型组体重差异无统计学意义(P>0.05),从第8~11周造模完成,模型组体重均显著低于正常组(P<0.01),模型组大鼠皮毛散乱、眯眼蜷卧,靠边,粪便性状变软或呈黄色稀便,肛门处常有粪便粘附;(2)粪便含水量:模型组在CUMS前后粪便含水量均较正常组明显升高(P<0.05);(3)旷场试验:模型组总穿行距离、中央区停留时间及平均速度均较正常组明显降低(P<0.01);(4)蔗糖水偏嗜试验:模型组大鼠对蔗糖水的偏嗜程度比正常组明显下降(P<0.01);(5)AWR:CUMS造模前后模型组AWR均显著低于正常组(P<0.01);(6)黏膜病理改变:苏木精-伊红染色发现正常组近端结肠黏膜结构完整,黏膜固有层没有炎性细胞浸润现象,模型组结肠黏膜固有层存在少量淋巴�Objective To establish a rat model of liver depression and spleen deficiency-syndrome irritable bowel syndrome with diarrhoea(IBS-D)based on the characteristics of traditional Chinese and Western medicine.The model was developed by superimposing three factors:neonatal mother-infant separation,chronic unpredictable multiple stress(CUMS),and trinitro-benzene-sulfonic acid(TNBS)-induced colitis.Methods Male offspring of pathogen-free(SPF)Sprague-Dawley(SD)pregnant rats were randomly divided into two groups:a normal group(n=8)and a model group(n=10).The model group was subjected to daily mother-infant separation for 3 hours from postnatal day 2 to day 14,after which they were reunited for feeding.The normal group received no such intervention and underwent weaning on day 22.Randomized separation of the litters began on day 30,continuing for 6 weeks,concluding the separation phase of the modeling.TNBS enema modeling began on day 1 of week 7,followed by 21 days of CUMS in week 9.Modeling was completed in week 11.The normal group remained untreated.After the CUMS phase,the liver depression symptoms were assessed via open field and sucrose preference tests,visceral sensitivity through the abdominal withdrawal reflex(AWR),diarrhoea severity by measuring fecal water content,and spleen deficiency symptoms by tracking body weight changes.Results①Body weight and general condition:At the end of the mother-infant separation phase,the model group had significantly lower body weights than the normal group(P<0.05).However,there were no significant differences between the two groups in week 7(before TNBS modeling)(P>0.05).From week 8 to week 11,the model group consistently exhibited lower body weights compared to the normal group(P<0.01).Model rats also displayed unkempt fur,squinting,side-leaning posture,soft or yellowish stools,and fecal adherence to the anus.②Fecal water content:The fecal water content in the model group was significantly higher than that of the normal group,both before and after CUMS(P<0.05).③Open field t

关 键 词：腹泻型肠易激综合征 模型评价 肝郁脾虚型 病证结合 

分 类 号：R574.4[医药卫生—消化系统]