模拟胃肠道反应器的参数建立与冷模实验研究

doi:10.11949/j.issn.0438-1157.20181488

化工学报 ›› 2019, Vol. 70 ›› Issue (5): 1879-1886.DOI: 10.11949/j.issn.0438-1157.20181488

模拟胃肠道反应器的参数建立与冷模实验研究

张文龙¹(),詹晓北¹,陈荦¹,郑志永^1,²(),朱莉³,李志涛¹,高敏杰¹

1. 江南大学生物工程学院糖化学与生物技术教育部重点实验室，江苏无锡 214122
2. 江南大学环境与土木工程学院，江苏无锡 214122
3. 无锡格莱克斯生物科技有限公司，江苏无锡 214125

收稿日期:2018-12-18 修回日期:2019-02-15 出版日期:2019-05-05 发布日期:2019-05-05
通讯作者: 郑志永
作者简介:<named-content content-type="corresp-name">张文龙</named-content>（1994—），男，硕士研究生，<email>bonapetite@163.com</email>|郑志永（1973—），男，博士，教授，<email>zhiyong@jiangnan.edu.cn</email>
基金资助:
国家重点研发计划重点专项项目(2017YFD0400302)

Parameter estimation and cold model experiments of gastrointestinal simulation reactor

Wenlong ZHANG¹(),Xiaobei ZHAN¹,Luo CHEN¹,Zhiyong ZHENG^1,²(),Li ZHU³,Zhitao LI¹,Minjie GAO¹

1. Key Laboratory of Carbohydrate Chemistry and Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, Jiangsu, China
2. School of Environment and Civil Engineering, Jiangnan University, Wuxi 214122, Jiangsu, China
3. Wuxi Glyco Biotechnology Co. Ltd., Wuxi 214125, Jiangsu, China

Received:2018-12-18 Revised:2019-02-15 Online:2019-05-05 Published:2019-05-05
Contact: Zhiyong ZHENG

摘要/Abstract

摘要：

体外消化和发酵实验紧密结合才能模拟完整消化道的功能，现有的模拟胃肠消化和大肠发酵的反应器结构各异且不通用，组合多个独立反应器则增加了实验的复杂程度和设备成本。集成了两类反应器的优势特征，开发了一种采用可编程逻辑控制器（PLC）的模拟胃肠道反应器（GSR），模拟了整体的胃肠道动态特征并与体内数据进行了比较。结果表明模拟胃肠道反应器既可准确模拟胃和小肠的蠕动、排空和混合等动态特征，又可提供肠道微生物的发酵环境。尾气排放和收集装置的设计实现了尾气快速排出和尾气体积的准确计量。模拟胃肠道反应器可为体外探索益生元对肠道微生物作用等研究提供帮助。

关键词: 胃肠道, 模拟, 反应器, PLC, 设计, 体外

Abstract:

In vitro digestion and fermentation experiments should be closely combined to simulate the function of the intact gastrointestinal tract. However, the existing simulated reactors for gastrointestinal digestion and large intestinal fermentation have different structures and are not universal. Combining the separated reactors would increase the complexity and the cost of the experiments. Integrated the dominant features of both types of reactors, a gastrointestinal simulation reactor(GSR) using a programmable logic controller(PLC) was developed in the present work. The dynamic characteristics of overall gastrointestinal tract were simulated and compared to the data in vivo. It shows that the developed reactor can accurately simulate the dynamic characteristics of peristalsis, emptying and mixing in the stomach and small intestine, and provide a fermentation environment for intestinal microbes. The exhaust gas discharge and collection device was considerately designed, the exhaust gas was quickly discharged and the volume could be accurately measured. The gastrointestinal simulation reactor can help to explore the role of prebiotics in intestinal microbes in vitro.

Key words: gastrointestinal tract, simulation, reactor, PLC, design, in vitro

中图分类号:

TQ 027.6

张文龙, 詹晓北, 陈荦, 郑志永, 朱莉, 李志涛, 高敏杰. 模拟胃肠道反应器的参数建立与冷模实验研究[J]. 化工学报, 2019, 70(5): 1879-1886.

Wenlong ZHANG, Xiaobei ZHAN, Luo CHEN, Zhiyong ZHENG, Li ZHU, Zhitao LI, Minjie GAO. Parameter estimation and cold model experiments of gastrointestinal simulation reactor[J]. CIESC Journal, 2019, 70(5): 1879-1886.

图/表 11

图1 GSR示意图

Fig.1 Schematic diagram of GSR

图2 尾气排放和收集装置

Fig.2 Exhaust gas discharge and collection device

图3 模拟胃蠕动过程中反应器内的压力变化

Fig.3 Pressure profiles in reactors during simulating gastric peristalsis

图4 模拟肠道蠕动波过程中GSR内的压力变化

Fig.4 Pressure profile in GSR during simulating intestinal peristaltic waves

图5 模拟胃和回肠的排空

Fig.5 Simulation of gastric and ileal emptying

表1 描述胃和回肠排空曲线的参数设置[7]

Table 1 Parameters to describe curves for gastric and ileal emptying[7]

模型	快排空		慢排空
模型	t _1/2/min	β	t _1/2/min	β
胃	35	1.15	70	2
回肠	85	1.4	160	1.6

表2 排空曲线的拟合参数

Table 2 Parameters for fitting emptying curve

模型	快排空			慢排空
模型	t _1/2/min	β	r ²	t _1/2/min	β	r ²
胃	35.09±0.18	1.18±0.01	0.9999	68.68±0.52	2.00±0.04	0.9995
回肠	84.10±0.03	1.43±0.00	0.9999	155.36±0.52	1.66±0.01	0.9997

表3 排空曲线与Elashoff’s模型的平均相对误差和平行实验的平均相对偏差

Table 3 Average relative error between emptying curve and Elashoff’s model and average relative deviation of parallel experiments

模型		快排空		慢排空
模型		相对误差/%	相对偏差/%	相对误差/%	相对偏差/%
GSR	胃	0.66	0.20	2.12	1.15
GSR	回肠	1.29	0.21	3.04	0.53
TIM-1^[7]	胃	0.51	2.73	5.18	6.12
TIM-1^[7]	回肠	5.16	6.32	9.32	11.67

图6 GSR的液体混合效果

Fig.6 Performance of liquid mixing in GSR

图7 GSR与TIM-2[8]内的短链脂肪酸残留率曲线

Fig.7 Percentage of short-chain fatty acids remaining in GSR and TIM-2

表4 反应器内的气体收集效果

Table 4 Performance of gas collection in GSR

注入空气体积/ml	气体停留时间/min	体积回收率/%
10.5	15.1±2.1	85.7±0.0
19.7	9.4±0.9	93.7±1.3
51.0	7.1±0.7	96.4±0.6

参考文献 30

1	伍鹏 . 体外仿生鼠胃消化系统的构建及其应用的研究[D]. 厦门: 厦门大学, 2016.Wu P. Study on development and application of in vitro biomimetic rat stomach digestive systems[D]. Xiamen: Xiamen University, 2016.
2	刘颖, 易涛, 宦娣, 等 . 脂质制剂体外动态肠吸收模型的建立及评价[J]. 药学学报, 2011, 46(8): 983-989.
	Liu Y , Yi T , Huan D , et al . Establishment and evaluation of a dynamic in vitro intestinal absorption model of lipid formulations[J]. Acta Pharmaceutica Sinica, 2011, 46(8): 983-989.
3	华慧颖, 闵玉涛, 宋彦显, 等 . 淀粉体外消化模型的构建及在交联淀粉消化研究中的应用[J]. 食品工业, 2011, (7): 19-22.
	Hua H Y , Min Y T , Song Y X , et al . Formation of starch digestion model and digestibilityof cross-linking starch in vitro[J]. The Food Industry, 2011, (7): 19-22.
4	邓人攀 . 基于仿生学原理的小肠模型反应器的设计和研究[D]. 厦门: 厦门大学, 2015.Deng R P. Design and research of the small intestine model reactor based on bionics principles[D]. Xiamen: Xiamen University, 2015.
5	李志杰 . 基于人的体外模拟胃消化系统的构建及评价[D]. 杭州: 浙江工商大学, 2017.Li Z J. Development and evaluation of human based artificial stomach digestion simulation system[D]. Hangzhou: Zhejiang Gongshang University, 2017.
6	Molly K , Vande Woestyne M , Verstraete W . Development of a 5-step multi-chamber reactor as a simulation of the human intestinal microbial ecosystem[J]. Applied Microbiology and Biotechnology, 1993, 39(2): 254-258.
7	Minekus M , Marteau P , Havenaar R , et al . A multicompartmental dynamic computer-controlled model simulating the stomach and small-intestine[J]. Alternatives to Laboratory Animals, 1995, 23(2): 197-209.
8	Minekus M , Smeets-Peeters M , Bernalier A , et al . A computer-controlled system to simulate conditions of the large intestine with peristaltic mixing, water absorption and absorption of fermentation products[J]. Applied Microbiology and Biotechnology, 1999, 53(1): 108-114.
9	Williams C F , Walton G E , Jiang L , et al . Comparative analysis of intestinal tract models[J]. Annual Review of Food Science and Technology, 2015, 6: 329-350.
10	Payne A N , Zihler A , Chassard C , et al . Advances and perspectives in in vitro human gut fermentation modeling[J]. Trends in Biotechnology, 2012, 30(1): 17-25.
11	Zheng Z Y , Chen Y Q , Zhan X B , et al . Mass transfer intensification in a novel airlift reactor assembly with helical sieve plates[J]. Chemical Engineering Journal, 2018, 342: 61-70.
12	刘明慧, 邹超, 肖杰, 等 . 基于仿生学的柔性反应器[J]. 化工学报, 2018, 69(1): 414-422.
	Liu M H , Zou C , Xiao J , et al . Soft-elastic bionic reactor[J]. CIESC Journal, 2018, 69(1): 414-422.
13	Maathuis A , Hoffman A , Evans A , et al . The effect of the undigested fraction of maize products on the activity and composition of the microbiota determined in a dynamic in vitro model of the human proximal large intestine[J]. Journal of the American College of Nutrition, 2009, 28(6): 657-666.
14	Elashoff J D , Reedy T J , Meyer J H . Analysis of gastric emptying data[J]. Gastroenterology, 1982, 83(6): 1306-1312.
15	李全阳, 夏文水 . 市场流行搅拌型酸奶流变学特性的初步研究[J]. 食品工业科技, 2003, 24(5): 43-47. Li Q Y , Xia W S . A primary study on the rheological properties of stirred yoghourt[J]. Science and Technology of Food Industry, 2003, 24(5): 43-47.
16	咸娜 . 黄原胶复配及流变学特性和应用研究[D]. 上海: 华东理工大学, 2017. Xian N . The rheological characteristics and application of xanthan gum and its hydrocolloids mixtures[D]. Shanghai: East China University of Science and Technology, 2017.
17	徐尧润, 刘玉军 . 牛奶流变性能研究[J]. 中国乳品工业, 1988, 16(5): 9-13. Xu Y R , Liu Y J . Studies on rheologic properties of cow milk[J]. China Dairy Industry, 1988, 16(5): 9-13.
18	许威 . 菊粉物化特性的研究[D]. 洛阳: 河南科技大学, 2012. Xu W . Study on physicochemical properties of inuiln[D]. Luoyang: Henan University of Science and Technology, 2012.
19	任妍娜 . 菊芋菊粉制取工艺优化及菊粉凝胶性质的研究[D]. 武汉: 武汉工业学院, 2011. Ren Y N . Research about preparation process optimization and gel properties of inulin[D]. Wuhan: Wuhan University of Technology, 2011.
20	Kozu H , Kobayashi I , Nakajima M , et al . Mixing characterization of liquid contents in human gastric digestion simulator equipped with gastric secretion and emptying[J]. Biochemical Engineering Journal, 2017, 122: 85-90.
21	Nowak A , Slizewska K , Otlewska A . Antigenotoxic activity of lactic acid bacteria, prebiotics, and products of their fermentation against selected mutagens[J]. Regulatory Toxicology and Pharmacology, 2015, 73(3): 938-946.
22	Bellmann S , Lelieveld J , Gorissen T , et al . Development of an advanced in vitro model of the stomach and its evaluation versus human gastric physiology[J]. Food Research International, 2016, 88: 191-198.
23	Ehrlein H , Scheemann M . Gastrointestinal motility[DB/OL]. Germany: Technische Universität München, 2005..
24	Smeets-Peeters M J , Minekus M , Havenaar R , et al . Description of a dynamic in vitro model of the dog gastrointestinal tract and an evaluation of various transit times for protein and calcium[J]. Alternatives to Laboratory Animals, 1999, 27(6): 935-949.
25	Bornhorst G M , Rutherfurd S M , Roman M J , et al . Gastric pH distribution and mixing of soft and rigid food particles in the stomach using a dual-marker technique[J]. Food Biophysics, 2014, 9(3): 292-300.
26	Marciani L , Gowland P A , Spiller R C , et al . Effect of meal viscosity and nutrients on satiety, intragastric dilution, and emptying assessed by MRI[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2001, 280(6): G1227-G1233.
27	Venema K . The TNO in vitro model of the colon (TIM-2)[M] //Verhoeckx K , Cotter P , López-Expósito I , et al . The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models. Cham: Springer International Publishing, 2015: 293-304.
28	Venema K , Van Nuenen M , Smeets-Peeters M , et al . TNO's in vitro large intestinal model: an excellent screening tool for functional food and pharmaceutical research[J]. Nutrition, 2000, 24(12): 558-564.
29	Gasson M J , Davies F L . High-frequency conjugation associated with Streptococcus lactis donor cell aggregation[J]. Journal of Bacteriology, 1980, 143(3): 1260-1264.
30	Chiu Y T , Stewart M . Comparison of konjac glucomannan digestibility and fermentability with other dietary fibers in vitro [J]. Journal of Medicinal Food, 2012, 15(2): 120-125.

[1]	叶展羽, 山訸, 徐震原. 用于太阳能蒸发的折纸式蒸发器性能仿真[J]. 化工学报, 2023, 74(S1): 132-140.
[2]	张龙, 宋孟杰, 邵苛苛, 张旋, 沈俊, 高润淼, 甄泽康, 江正勇. 管翅式换热器迎风侧翅片末端霜层生长模拟研究[J]. 化工学报, 2023, 74(S1): 179-182.
[3]	张义飞, 刘舫辰, 张双星, 杜文静. 超临界二氧化碳用印刷电路板式换热器性能分析[J]. 化工学报, 2023, 74(S1): 183-190.
[4]	王志国, 薛孟, 董芋双, 张田震, 秦晓凯, 韩强. 基于裂隙粗糙性表征方法的地热岩体热流耦合数值模拟与分析[J]. 化工学报, 2023, 74(S1): 223-234.
[5]	宋嘉豪, 王文. 斯特林发动机与高温热管耦合运行特性研究[J]. 化工学报, 2023, 74(S1): 287-294.
[6]	张思雨, 殷勇高, 贾鹏琦, 叶威. 双U型地埋管群跨季节蓄热特性研究[J]. 化工学报, 2023, 74(S1): 295-301.
[7]	刘远超, 关斌, 钟建斌, 徐一帆, 蒋旭浩, 李耑. 单层XSe₂（X=Zr/Hf）的热电输运特性研究[J]. 化工学报, 2023, 74(9): 3968-3978.
[8]	陈哲文, 魏俊杰, 张玉明. 超临界水煤气化耦合SOFC发电系统集成及其能量转化机制[J]. 化工学报, 2023, 74(9): 3888-3902.
[9]	宋明昊, 赵霏, 刘淑晴, 李国选, 杨声, 雷志刚. 离子液体脱除模拟油中挥发酚的多尺度模拟与研究[J]. 化工学报, 2023, 74(9): 3654-3664.
[10]	胡建波, 刘洪超, 胡齐, 黄美英, 宋先雨, 赵双良. 有机笼跨细胞膜易位行为的分子动力学模拟研究[J]. 化工学报, 2023, 74(9): 3756-3765.
[11]	赵佳佳, 田世祥, 李鹏, 谢洪高. SiO₂-H₂O纳米流体强化煤尘润湿性的微观机理研究[J]. 化工学报, 2023, 74(9): 3931-3945.
[12]	齐聪, 丁子, 余杰, 汤茂清, 梁林. 基于选择吸收纳米薄膜的太阳能温差发电特性研究[J]. 化工学报, 2023, 74(9): 3921-3930.
[13]	何松, 刘乔迈, 谢广烁, 王斯民, 肖娟. 高浓度水煤浆管道气膜减阻两相流模拟及代理辅助优化[J]. 化工学报, 2023, 74(9): 3766-3774.
[14]	邢雷, 苗春雨, 蒋明虎, 赵立新, 李新亚. 井下微型气液旋流分离器优化设计与性能分析[J]. 化工学报, 2023, 74(8): 3394-3406.
[15]	韩晨, 司徒友珉, 朱斌, 许建良, 郭晓镭, 刘海峰. 协同处理废液的多喷嘴粉煤气化炉内反应流动研究[J]. 化工学报, 2023, 74(8): 3266-3278.

模拟胃肠道反应器的参数建立与冷模实验研究

Parameter estimation and cold model experiments of gastrointestinal simulation reactor

RichHTML

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

图/表 11

参考文献 30

相关文章 15

编辑推荐

Metrics

本文评价