Wu Haomeng, Zhan Kai, Rao Kehan, Zheng Huan, Qin Shumin, Tang Xudong, Huang Shaogang
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China; The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China; Collaborative Innovation Team of Traditional Chinese Medicine in Prevention and Treatment of Functional Gastrointestinal Diseases, Guangzhou 510120, China.
The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
Biomed Pharmacother. 2022 May;149:112811. doi: 10.1016/j.biopha.2022.112811. Epub 2022 Mar 15.
The brain-gut-microbiota (BGM) axis is known to be essential for diarrhea-predominant irritable bowel syndrome (IBS-D). In order to evaluate the effects of IBS-D rat models (the central sensitization model, the peripheral sensitization model and the compound model) on the BGM axis, five models were induced in Wistar rats with 4% acetic acid (AD, dissolved 0.4 ml of AD in 9.6 ml of ultrapure water) + wrap restrain stress (WRS), 4% AD, colorectal distention (CRD), WRS, and neonatal maternal separation (NMS). Abdominal withdrawal reflex (AWR) scale scores and the moisture content of feces (MCF) were evaluated on the day of completing modeling. Body weight was measured every 7 days during modeling. Brain gut peptides, cytokine levels, the activity of spinal cord neurons, intestinal mucosal barrier function, and gut microbiota were determined after induction of IBS-D. We found intervention with 4% AD + WRS, 4% AD, CRD, WRS, and NMS induced a similar course of effects on the BGM axis. Among the five models, AWR scores (60 mmHg, 80 mmHg) were all increased. The levels of 5-hydroxytryptamine, corticotropin-releasing factor, substance P, and calcitonin gene-related protein in serum rapidly increased, whereas that of neuropeptide Y decreased. C-fos in the spinal cord showed increased neuronal activity. The intestinal permeability was increased and the composition and structure of gut microbiota were changed. In conclusion, the five models could cause changes in BGM axis, but the 4% AD + WRS model was closer to the changes BGM axis of post-inflammatory models of IBS-D.
脑-肠-微生物群（BGM）轴已知对腹泻型肠易激综合征（IBS-D）至关重要。为了评估IBS-D大鼠模型（中枢敏化模型、外周敏化模型和复合模型）对BGM轴的影响，用4%乙酸（AD，将0.4 ml AD溶解于9.6 ml超纯水中）+束缚应激（WRS）、4% AD、结肠扩张（CRD）、WRS和新生鼠母婴分离（NMS）在Wistar大鼠中诱导出五种模型。在完成建模当天评估腹部撤回反射（AWR）量表评分和粪便水分含量（MCF）。建模期间每7天测量一次体重。在诱导IBS-D后测定脑肠肽、细胞因子水平、脊髓神经元活性、肠黏膜屏障功能和肠道微生物群。我们发现用4% AD + WRS、4% AD、CRD、WRS和NMS进行干预对BGM轴产生了相似的效应过程。在这五种模型中，AWR评分（60 mmHg、80 mmHg）均升高。血清中5-羟色胺、促肾上腺皮质激素释放因子、P物质和降钙素基因相关蛋白水平迅速升高，而神经肽Y水平降低。脊髓中的C-fos显示神经元活性增加。肠道通透性增加，肠道微生物群的组成和结构发生改变。总之，这五种模型均可引起BGM轴的变化，但4% AD + WRS模型更接近IBS-D炎症后模型的BGM轴变化。
