基于综合因素刺激的肠易激综合征模型构建方法学研究

doi:10.5246/jcps.2023.03.015

中国药学(英文版) ›› 2023, Vol. 32 ›› Issue (3): 180-189.DOI: 10.5246/jcps.2023.03.015

基于综合因素刺激的肠易激综合征模型构建方法学研究

邹鑫峰¹, 郭海华¹, 邓樑钧¹, 杨淯婷¹, 袁正强¹^,^*(), 谭文²^,³^,^*()

1. 广东工业大学生物医药学院, 广东广州 510006
2. 暨南大学沅芷健康科技有限公司博士后创新基地, 广东珠海 519000
3. 蒙纳什大学马来西亚校区, Jeffrey Cheah医学与健康学院, 马来西亚圣威班达尔 47500

收稿日期:2022-09-26 修回日期:2022-10-27 接受日期:2022-11-28 出版日期:2023-03-31 发布日期:2023-03-30
通讯作者: 袁正强, 谭文
作者简介:
+ Tel.: +86-13928954505, E-mail: scut_gdut@163.com
+ E-mail: yuanzq@gdut.edu.cn

A study of irritable bowel syndrome model construction based on combined factor stimulation

Xinfeng Zou¹, Haihua Guo¹, Liangjun Deng¹, Yuting Yang¹, Zhengqiang Yuan¹^,^*(), Wen Tan²^,³^,^*()

1 School of Biomedical and Pharmaceutical Science, Guangdong University of Technology, Guangzhou 510006, China
2 Post-Doctoral Innovation Site, Jinan University Affiliation, YuanZhi Health Technology Co., LTD., Hengqing New District, Zhuhai, Guangdong 519000, China
3 Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Malaysia

Received:2022-09-26 Revised:2022-10-27 Accepted:2022-11-28 Online:2023-03-31 Published:2023-03-30
Contact: Zhengqiang Yuan, Wen Tan

摘要/Abstract

摘要：

为了建立一个建模周期短且符合IBS发病机制的模型, 我们将慢性不可预知刺激与化学刺激相结合, 建立一种新的肠易激综合征模型, 并探讨其可行性。以慢性不可预测刺激为单因素模型, 慢性不可预测刺激加冰醋酸刺激为综合因素模型。从体重增长率、基本食物消耗量、蔗糖消耗量、粪便颗粒数、Bristol分值、腹部回撤反射、旷场实验、高架十字迷宫试验、肠道运输时间、HE染色等一系列试验中分析了肠易激综合征模型的症状。结果显示, 与单因素模型和对照组相比, 综合因素组模型中的大鼠体重增加较少、食物消耗、蔗糖消耗减少、粪便颗粒数增加、Bristol评分和疼痛阈值下降、运动量大大减少。由于综合刺激对大鼠模型有明显的作用, 综合因素组模型更加符合IBS复杂的发病机制, 可用于建立有效的IBS模型。与雌性大鼠相比, 雄性大鼠的造模效果明显。

关键词: 肠易激综合征, 大鼠模型, 焦虑, 综合因素

Abstract:

To establish a model with a short modeling period and consistent with the pathogenesis of IBS, chronic stimulation and chemical stimulation were combined. In the present study, we aimed to establish a novel model of irritable bowel syndrome (IBS) and investigate its feasibility. Chronic unpredictable stimulation was used as a single factor model, and its addition with glacial acetic acid stimulation was used as a comprehensive factor model. The symptoms of the IBS model were analyzed from a collection of tests, including body weight, essential food consumption, sucrose consumption, fecal grain number, Bristol score, abdominal withdrawal reflex, open field tests, elevated cross-maze tests, intestinal transportation time, and H&E staining. The results showed that compared with the single-factor model and the control groups, the rats in the comprehensive model group exhibited less body weight, reduced food consumption, decreased sucrose consumption, increased fecal grain number, decreased Bristol score and pain threshold, and significantly reduced physical activity. The comprehensive factor group model conformed to the complex pathogenesis of IBS and thus had a significant effect on it, which could be used to establish an effective IBS model.?Furthermore, the modeling effect was significantly evident in male rats compared with female ones.

Key words: Irritable bowel syndrome, Rat model, Anxiety, Comprehensive factors

Supporting:

邹鑫峰, 郭海华, 邓樑钧, 杨淯婷, 袁正强, 谭文. 基于综合因素刺激的肠易激综合征模型构建方法学研究[J]. 中国药学(英文版), 2023, 32(3): 180-189.

Xinfeng Zou, Haihua Guo, Liangjun Deng, Yuting Yang, Zhengqiang Yuan, Wen Tan. A study of irritable bowel syndrome model construction based on combined factor stimulation[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(3): 180-189.

图/表 10

Figure 1. Changes in body weight gain of rats. The weight gain of the rats after modeling was divided by the weight of the rats on the first day of the experiment. Blank-Male is abbreviated to Blank-M, male rats were modeled by single factor stimulation and abbreviated as Model 1-M, male rats were modeled by combined factor stimulation and abbreviated as Model 2-M, Blank-Female is abbreviated to Blank-F, female rats were modeled by single factor stimulation and abbreviated as Model 1-F, female rats were modeled by combined factor stimulation and abbreviated as Model 2-F. n = 6 rat per group. Data were represented as mean ± SD. *P < 0.05; ****P < 0.0001; vs. Blank group.

Figure 2. Basic food consumption of rats. The rats were housed in single cages and the feed consumption of the rats was measured on the last day. n = 6 rat per group. Data were represented as mean ± SD. *P < 0.05, **P < 0.01, ****P < 0.0001; vs. Blank group.

Figure 3. The number of dejection amounts in rats. The rats were fed separately, one per cage, placed in a quiet environment and the number of fecal pellets counted over an 8 h period. n = 6 rat per group. Data were represented as mean ± SD. *P < 0.05; vs. Blank group.

Figure 4. Score diagram of Bristol rats. The fecal pellets were collected for scoring. Bristol grading criteria were used. Grade 1: scattered hard blocks, like nuts; Grade 2: sausage-shaped, but lumped; Grade 3: sausage-shaped, but with cracks on the surface; Grade 4: like sausage or snake, smooth and soft; Grade 5: soft mass and clear edge; Grade 6: fluffy, unclear edge and mushy stool; Grade 7: water sample, no solid substance. n = 6 rat per group. Data were represented as mean ± SD. *P < 0.05; **P < 0.01; vs. Blank group.

Figure 5. Physiological salt amount in rats. The F12 catheter was connected to a 5-mL syringe, and then a balloon coated with open-cell solution was inserted into the rat’s anus for about 1.0 cm. The operator randomly injected saline into the balloon rapidly and maintained it for 20 s after reaching the maximum arched back (the maximum arched back state of the rat is the body in an arched position and the pelvis raised), and repeatedly injected saline three times with an interval of 4 min. n = 6 rat per group. Data were represented as mean ± SD. **P < 0.01; vs. Blank group.

Figure 6. ITT diagram of rats. The activated carbon powder was injected into the stomach and mixed with normal saline in proportion, and the time from the beginning of intragastric administration to the discharge of the first black feces was recorded. n = 6 rat per group. Data were represented as mean ± SD. *P < 0.05; **P < 0.01; ****P < 0.0001; vs. Blank group.

Figure 7. 2% Sucrose consumption: compared with the blank group, the sugar water consumption of rats in model 1 and 2 groups was significantly lower.

Figure 8. Open field experiment results of rats. A–D: Upright times, stationary time, total distance, and central area activity time of rats in the open field experiment. n = 4–6 rat per group. Data were represented as mean ± SD. *P < 0.05; **P < 0.01; ****P < 0.0001; vs. Blank group.

Figure 9. Results of rat elevated cross maze. A–B: Percentage of time to open the arm, percentage of the number of times to open the arm. n = 4–6 rat per group. Data were represented as mean ± SD. *P < 0.05; **P < 0.01; ****P < 0.0001; vs. Blank group.

Figure 10. Pathology of conventional H&E staining in rats. From left to right: H&E staining pathological maps of rats in the control group (male), single factor group (male), combined factor group (male), control group (female), single factor group (female), and combined factor group (female).

参考文献 15

[1]	Weerts, Z.Z.R.M.; Essers, B.A.B.; Jonkers, D.M.A.E.; Willems, J.I.A.; Janssen, D.J.P.A.; Witteman, B.J.M.; Clemens, C.H.M.; Westendorp, A.; Masclee, A.A.M.; Keszthelyi, D. A trial-based economic evaluation of peppermint oil for the treatment of irritable bowel syndrome. United Eur. Gastroenterol. J. 2021, 9, 997–1006.
[2]	Zhao, J.; Chen, M.; Wang, X.; Ye, K.; Shi, S.; Li, H.; Wang, J.; Chen, X.; Ni, J.; Wei, Q.; Shi, Y.; Hu, Y.; Sun, J.; Li, D.; Liu, S.; Li, Z.; Zheng, H.; Yu, S.G. Efficacy of acupuncture in refractory irritable bowel syndrome: study protocol for a randomised controlled trial. BMJ Open. 2021, 11, e045655.
[3]	Shah, A.; Gurusamy, S.R.; Hansen, T.; Callaghan, G.; Talley, N.J.; Koloski, N.; Walker, M.M.; Jones, M.P.; Morrison, M.; Holtmann, G.J. Concomitant irritable bowel syndrome does not influence the response to antimicrobial therapy in patients with functional dyspepsia. Dig. Dis. Sci. 2022, 67, 2299–2309.
[4]	Bonetto, S.; Fagoonee, S.; Battaglia, E.; Grassini, M.; Saracco, G.; Pellicano, R. Recent advances in the treatment of irritable bowel syndrome. Polish Arch. Intern. Med. 2021, 131, 709–715.
[5]	Fairbrass, K.M.; Selinger, C.P.; Gracie, D.J.; Ford, A.C. Prevalence and impact of Rome IV versus Rome III irritable bowel syndrome in patients with inflammatory bowel disease. Neurogastroenterol. Motil. 2022, 34, e14256.
[6]	Chen, G.R.; Xie, X.F.; Peng, C. Treatment of irritable bowel syndrome by Chinese medicine: a review. Chin. J. Integr. Med. 2021, 1–8.
[7]	Zhang, F.; Xiang, W.; Li, C.Y.; Li, S.C. Economic burden of irritable bowel syndrome in China. World J. Gastroenterol. 2016, 22, 10450–10460.
[8]	Shen, T.A.; Wu, X.H.; Feng, J.W.; Zhang, Z.N.; Wang, M.Y. Opposite sex contact and isolation to simultaneously prepare female and male depression/anxiety model rats. Acta Acad. Med. Wannan. 2019, 38, 9–11, 20.
[9]	Zyoud, S.H.; Smale, S.; Waring, W.S.; Sweileh, W.; Al-Jabi, S.W. Global research trends in the microbiome related to irritable bowel syndrome: a bibliometric and visualized study. World J. Gastroenterol. 2021, 27, 1341–1353.
[10]	Traini, C.; Idrizaj, E.; Garella, R.; Faussone-Pellegrini, M.S.; Baccari, M.C.; Vannucchi, M.G. Otilonium Bromide treatment prevents nitrergic functional and morphological changes caused by chronic stress in the distal colon of a rat IBS model. J. Cell Mol. Med. 2021, 25, 6988–7000.
[11]	Bravo, J.A.; Dinan, T.G.; Cryan, J.F. Alterations in the central CRF system of two different rat models of comorbid depression and functional gastrointestinal disorders. Int. J. Neuropsychopharmacol. 2011, 14, 666–683.
[12]	O’Malley D.; Dinan T.G.; Cryan J.F. Neonatal maternal separation in the rat impacts on the stress responsivity of central corticotropin-releasing factor receptors in adulthood. Psychopharmacology. 2011, 2141, 221–229.
[13]	O’Mahony, S.M.; Marchesi, J.R.; Scully, P.; Codling, C.; Ceolho, A.M.; Quigley, E.M.; Cryan, J.F.; Dinan, T.G. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol. Psychiatry. 2009, 65, 263–267.
[14]	Santos, T.; Baungratz, M.M.; Haskel, S.P.; de Lima, D.D.; da Cruz, J.N.; Magro, D.D.; da Cruz, J.G. Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression. Neuropsychiatr. Dis. Treat. 2012, 8, 413–422.
[15]	Klibaite, U.; Kislin, M.; Verpeut, J.L.; Bergeler, S.; Sun, X.; Shaevitz, J.W.; Wang, S.S. Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models. Mol. Autism. 2022, 13, 12.

基于综合因素刺激的肠易激综合征模型构建方法学研究

A study of irritable bowel syndrome model construction based on combined factor stimulation

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