慢性避水应激法建立大鼠肠易激综合征模型及其评价

doi:10.13481/j.1671-587X.20240331

Abstract

Abstract:

Objective To discuss the method for establishing the rat models of irritable bowel syndrome （IBS） by chronic water avoidance stress （WAS） method， and to evaluate its feasibility. Methods Thirty male Wistar rats were randomly divided into control group （n=10） and model group （n=20）. The rats in model group were induced by WAS method for 1 h everyday， lasting for 10 consecutive days； the rats in control group underwent no interventions. After modeling， the general conditions and body weights of the rats in two groups were observed and recorded. The elevated plus maze （EPM） test was used to detect the percentages of the number of open arm entries （OE） and the time spent in open arms （OT） of the rats in two groups；the abdominal withdrawal reflex （AWR） test was used to assess the visceral sensitivity of the rats in two groups； electrocardiography was used to detect the heart rate variability （HRV） of the rats in two groups； electromyography （EMG） of the external oblique muscle was used to detect the colorectal pain sensitivity thresholds of the rats in two groups； multi-channel physiological signal recorder was used to monitor the slow wave frequency of the colon of the rats in two groups. Results There were no death rats in both groups during the modeling period. After modeling， the rats in model group exhibited poor mental status， reduced spontaneous activity， hypoactivity， disordered and dull fur， irritability， and unclean anal areas； whereas， the rats in control group showed no significant changes in the mental state， spontaneous activity， fur， and perianal area. Compared with control group， the body weight of the rats in model group was significantly decreased （P<0.05）. The EPM test results showed that compared with control group， the OE percentage and OT percentage of the rats in model group were significantly decreased （P<0.01）. The AWR test results showed that 12 rats in model group scored ≥3 points， indicating that the successful rate in creating the visceral pain models was 60%. Compared with control group， the low frequency （LF） signals and the ratio of LF/high frequency （HF） of the rats in model group were significantly increased （P<0.01）， and the HF was significantly decreased （P<0.05）. The EMG results showed that compared with control group， the coloretal pain sensitivity threshold of the colon of the rats in model group was significantly decreased （P<0.01）， and the slow wave frequency of the colon was significantly increased （P<0.01）. Conclusion The WAS method for establishing the rat model of IBS effectively demonstrates the changes in behavior and mental state， increased the visceral sensitivity， accelerated colonic slow wave frequency， and autonomic nervous system imbalance； the WAS method can serve as an effective modeling approach for observing and evaluating the related drugs and interventions on treatment of IBS.

Key words: Irritable bowel syndrome, Ethology, Visceral hypersensitivity, Colonic function, Autonomic nervous system balance

CLC Number:

R574.4

Tingting LIU,Qingyu ZHANG,Xiangshun ZHAO,Yunlai SHI,Yannan YU,Zhengwen WANG,Shaozong CHEN,Chuwen FENG,Tiansong YANG. Establishment of irritable bowel syndrome model in rats by chronic water avoidance stress method and its evaluation[J].Journal of Jilin University(Medicine Edition), 2024, 50(3): 840-846.

Figures/Tables 4

References 32

1	MAYER E A， RYU H J， BHATT R R. The neurobiology of irritable bowel syndrome［J］. Mol Psychiatry， 2023， 28（4）： 1451-1465.
2	DROSSMAN D A. Functional gastrointestinal disorders： history， pathophysiology， clinical features and Rome Ⅳ［J］. Gastroenterology， 2016. DOI： 10.1053/j.gastro.2016.02.032 . doi: 10.1053/j.gastro.2016.02.032
3	WU J， CHENG Y， ZHANG R， et al. P2Y1R is involved in visceral hypersensitivity in rats with experimental irritable bowel syndrome［J］. World J Gastroenterol， 2017， 23（34）： 6339-6349.
4	管洁，邓娜，蔺晓源，等. 腹泻型肠易激综合征及其中医病证结合动物模型的研究进展［J］. 中医药信息， 2023， 40（5）： 73-78.
5	杨清瑞，胡泽玉，杜晓泉，等. 腹泻型肠易激综合征中医病证结合动物模型研究［J］. 中国中医基础医学杂志， 2021， 27（12）： 1981-1984.
6	JOHNSON A C， FARMER A D， NESS T J， et al. Critical evaluation of animal models of visceral pain for therapeutics development： a focus on irritable bowel syndrome［J］. Neurogastroenterol Motil， 2020， 32（4）： e13776.
7	赵迎盼，唐旭东，卞兆祥，等. IBS-D肝郁脾虚型病证症结合大鼠模型的建立与评价的初步研究［J］. 中国中西医结合杂志， 2013， 33（11）： 1507-1514.
8	MAYER E A， BRADESI S， CHANG L， et al. Functional GI disorders： from animal models to drug development［J］. Gut， 2008， 57（3）： 384-404.
9	张方，翁志军，吴璐一，等. 病因相关肠易激综合征动物模型研究进展［J］. 世界华人消化杂志， 2018， 26（30）： 1772-1777.
10	TRAINI C， IDRIZAJ E， GARELLA R， et al. Otilonium Bromide treatment prevents nitrergic functional and morphological changes caused by chronic stress in the distal colon of a rat IBS model［J］. J Cell Mol Med， 2021， 25（14）： 6988-7000.
11	HONG K B， SEO H， LEE J S， et al. Effects of probiotic supplementation on post-infectious irritable bowel syndrome in rodent model［J］. BMC Complement Altern Med， 2019， 19（1）： 195.
12	曾威，奚庆华，吴至久男. 肠易激综合征动物模型的研制现状和进展［J］. 现代医药卫生， 2016， 32（17）： 2658-2661.
13	贺星，刘卫，唐郡，等. 腹泻型肠易激综合征动物模型建立及评价［J］. 胃肠病学和肝病学杂志， 2020， 29（12）： 1386-1390.
14	王宁，纪昌春，万鹏，等. 病证结合模式下腹泻型肠易激综合征实验动物模型的研究进展［J］. 天津中医药大学学报， 2021， 40（4）： 533-538.
15	吴嫣然. 痛泻要方对慢性应激导致的内脏高敏感和肠道动力异常的作用及机制研究［D］. 武汉：华中科技大学， 2016.
16	胡莹，郑依玲，梅全喜，等. 痛泻要方破壁饮片对慢性避水应激大鼠内脏高敏感性的调节作用［J］. 中药新药与临床药理， 2021， 32（3）： 322-331.
17	何苏月，马卓琳，范昕然，等. 机械敏感性离子通道Piezo1参与慢性避水应激肠易激综合征大鼠内脏高敏感性和5-羟色胺代谢异常［J］. 中国病理生理杂志， 2021， 37（4）： 577-585.
18	余光，全晓静，唐勤彩，等. P物质与慢性应激诱导的大鼠结肠动力紊乱的关系及其机制［J］. 武汉大学学报（医学版）， 2016， 37（3）： 407-410.
19	MAYER E A， NALIBOFF B D， CHANG L， et al. V. Stress and irritable bowel syndrome［J］. Am J Physiol Gastrointest Liver Physiol， 2001， 280（4）：G519-G524.
20	白涛，宋军，侯晓华. 神经调控通路在肠易激综合征内脏高敏感发病机制中作用的研究进展［J］. 胃肠病学， 2016， 21（6）： 362-365.
21	CAO G P， GUI D， FU L D， et al. Anxiolytic and neuroprotective effects of the Traditional Chinese Medicinal formulation Dan-Zhi-Xiao-Yao-San in a rat model of chronic stress［J］. Mol Med Rep， 2016， 14（2）： 1247-1254.
22	黄海阳，冼绍祥，杨忠奇. 温胆片对高架十字迷宫实验大鼠脑组织神经递质GABA、Glu含量的影响［J］. 中药新药与临床药理， 2015， 26（5）： 631-635.
23	YANG J M， XIAN Y F， IP P S， et al. Schisandra chinensis reverses visceral hypersensitivity in a neonatal-maternal separated rat model［J］. Phytomedicine， 2012， 19（5）： 402-408.
24	TAO E F， LONG G， YANG T， et al. Maternal separation induced visceral hypersensitivity evaluated via novel and small size distention balloon in post-weaning mice［J］. Front Neurosci， 2022， 15： 803957.
25	GUARINO M P， BARBARA G， CICENIA A， et al. Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility［J］. Neurogastroenterol Motil， 2017， 29（2）： 1-9.
26	SZUCS K F， NAGY A， GROSZ G， et al. Correlation between slow-wave myoelectric signals and mechanical contractions in the gastrointestinal tract： advanced electromyographic method in rats［J］. J Pharmacol Toxicol Methods， 2016， 82： 37-44.
27	SHAFIK A， EL-SIBAI O， SHAFIK A A， et al. Electric activity of the colon in irritable bowel syndrome： the ‘tachyarrhythmic’ electric pattern ［J］. J Gastroenterol Hepatol， 2004， 19（2）： 205-210.
28	MAZURAK N， SEREDYUK N， SAUER H， et al. Heart rate variability in the irritable bowel syndrome： a review of the literature［J］. Neurogastroenterol Motil， 2012， 24（3）： 206-216.
29	LIU Z M， CHEN T， WEI K M， et al. Similarity changes analysis for heart rate fluctuation regularity as a new screening method for congestive heart failure［J］. Entropy， 2021， 23（12）： 1669.
30	苏晓兰，魏玮. 肠易激综合征动物模型研究进展［J］. 山东中医杂志， 2013， 32（2）： 133-135.
31	任杰，陆敏. 肠易激综合征动物模型的研究进展［J］. 中国医药导报， 2016， 13（27）： 47-50.
32	刘新明，刘斯文，刘书芹，等. 病证结合的肠易激综合征动物模型研究进展［J］. 吉林中医药， 2022， 42（1）： 116-119.

Group	LF（η/%）	HF（η/%）	LF/HF
Control	1.81±0.47	69.79±15.05	0.02±0.01
Model	2.89±0.50^**	46.65±2.65^*	0.06±0.01^**

Establishment of irritable bowel syndrome model in rats by chronic water avoidance stress method and its evaluation

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 4

References 32

Related Articles 1

Metrics

Comments

Recommended 0