A modeling method for establishing an experimental animal model of digestive dysfunction in the late stage of severe acute pancreatitis_West China Medical Journal

Authors：

LONG Dan ¹ , YANG Xijing ² , WEI Liying ³ , GAO Rongmei ³ , YANG Yuqing ³ , ZHANG Dongmei ³ , YI Xiaolin ⁴ , ZHANG Yumei ⁵ ,  HU Jing ⁶

1. Transplant Center and NHC Key Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Animal Experiment Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. Department of Hepatobiliary, Pancreatic and Splenic Surgery and Department of Clinical Lab, Leshan Hospital of Traditiongal Chinese Medicine, Leshan, Sichuan 614000, P. R. China;
4. Integrated Traditional Chinese and Western Medicine Internal Medicine, Shang Jin Hospital of West China Hospital, Chengdu, Sichuan 611730, P. R. China;
5. Department of Traditional Chinese Medicine Department, Xiang’an Hospital of Xiamen University, Xiamen, Fujian 361000, P. R. China;
6. Department of Spieen, Stomach and Brain Diseases, Neijian Hospital of Traditional Chinese Medicine, Neijiang, Sichuan 641000, P. R. China;

Corresponding?author：

HU Jing, Email: 497645416@qq.com

Keywords：

Severe acute pancreatitis; pancreatic exocrine insufficiency and pancreatic endocrine disfunction; decreased digestive function; experimental animal model; rat

DOI：

10.7507/1002-0179.202410116

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Objective To establish a modeling method for an animal model simulating the decline of digestive function after a large amount of tissue necrosis of the pancreas due to acute injury after severe acute pancreatitis (SAP). Methods Twenty male SD rats were randomly divided into the model group and the sham operation group according to the random number table method, with 10 rats in each group. First, the SAP model was established by retrograde bile duct injection of sodium taurocholate in the model group, whereas the sham operation group received physiological saline injection. Fluid infusion began 2 hours later, twice a day, with an 8-hour interval, for 2 days. The traditional Chinese medicine Dachengqi Decoction without Decoction Granules was formulated into a suspension in proportion and administered by gavage once at 18 hours and once at 24 hours after the operation to ensure the blood volume of rats and reduce inflammatory damage. Normal drinking water was allowed 48 hours after modeling. After 72 hours, ordinary feed was given for feeding. The feeding lasted for 14 days (the total duration of the experiment was 17 days). The body weight, vitality status and stool characteristics of the rats were observed and recorded on the day of open feed feeding and 14 days later. Fourteen days after feeding, the animals were sacrificed and samples were collected for examination of blood glucose, fecal elastase and hematoxylin-eosin staining pathological scores. Results All 10 rats in the model group were successfully modeled with a 100% survival rate. The body weight of rats in the model group 14 days after ordinary feeding was lower than that on the day of open diet [(180.80±4.39) vs. (222.90±6.14) g, P<0.001], and lower than that of rats in the sham operation group 14 days later [(180.80±4.39) vs. (221.70±7.45) g, P<0.001]. Compared with the sham operation group, inflammatory cell infiltration injury still existed in the pancreatic tissue of the model group, and some pancreatic tissues showed pathologically related changes of chronic injury. The pathological score of the model group was higher than that of the sham operation group [7.5 (7, 9) vs. 0 (0, 0), P<0.001]; the blood glucose concentration increased [(13.000±1.531) vs. (8.070±0.851) mmol/L, P<0.001]. The secretion of fecal elastase, a metabolite of trypsin in vivo, was significantly decreased [(5.451±0.936) vs. (8.593±1.105) mg/mL, P<0.001]. Conclusion The use of short-term liquid supplementation, traditional Chinese medicine anti-inflammatory treatment, and early dietary stimulation can effectively combat early severe inflammatory damage in SAP, protect the life of model rats, and enable them to survive and experience digestive dysfunction, thus establishing an experimental animal model of digestive dysfunction in the late stage of SAP.

Citation： LONG Dan, YANG Xijing, WEI Liying, GAO Rongmei, YANG Yuqing, ZHANG Dongmei, YI Xiaolin, ZHANG Yumei, HU Jing. A modeling method for establishing an experimental animal model of digestive dysfunction in the late stage of severe acute pancreatitis. West China Medical Journal, 2025, 40(11): 1813-1818. doi: 10.7507/1002-0179.202410116 Copy

1.	Beger HG, Rau BM. Severe acute pancreatitis: clinical course and management. World J Gastroenterol, 2007, 13(38): 5043-5051.
2.	Italian Association for the Study of the Pancreas (AISP), Pezzilli R, Zerbi A, et al. Consensus guidelines on severe acute pancreatitis. Dig Liver Dis, 2015, 47(7): 532-543.
3.	姚佳心, 黃會芳, 付澤花. 腫塊型慢性胰腺炎與胰腺癌的鑒別診斷. 胃腸病學和肝病學雜志, 2025, 34(1): 148-153.
4.	Rasmussen HH, Irtun O, Olesen SS, et al. Nutrition in chronic pancreatitis. World J Gastroenterol, 2013, 19(42): 7267-7275.
5.	Chowdhury RS, Forsmark CE. Review article: pancreatic function testing. Aliment Pharmacol Ther, 2003, 17(6): 733-750.
6.	Hollemans RA, Hallensleben NDL, Mager DJ, et al. Pancreatic exocrine insufficiency following acute pancreatitis: systematic review and study level meta-analysis. Pancreatology, 2018, 18(3): 253-262.
7.	Wu D, Xu Y, Zeng Y, et al. Endocrine pancreatic function changes after acute pancreatitis. Pancreas, 2011, 40(7): 1006-1011.
8.	Hamada S, Matsumoto R, Masamune A. Pancreatic stellate cells and metabolic alteration: physiology and pathophysiology. Front Physiol, 2022, 13: 865105.
9.	Fonseca Sepúlveda EV, Guerrero-Lozano R. Acute pancreatitis and recurrent acute pancreatitis: an exploration of clinical and etiologic factors and outcomes. J Pediatr (Rio J), 2019, 95(6): 713-719.
10.	Balint ER, Fur G, Kiss L, et al. Assessment of the course of acute pancreatitis in the light of aetiology: a systematic review and meta-analysis. Sci Rep, 2020, 10(1): 17936.
11.	Su YR, Hong YP, Mei FC, et al. High-fat diet aggravates the intestinal barrier injury via TLR4-RIP3 pathway in a rat model of severe acute pancreatitis. Mediators Inflamm, 2019, 2019: 2512687.
12.	Hu J, Zhang YM, Miao YF, et al. Effects of Yue-Bi-Tang on water metabolism in severe acute pancreatitis rats with acute lung-kidney injury. World J Gastroenterol, 2020, 26(43): 6810-6821.
13.	Zhao X, Zhang Y, Li J, et al. Tissue pharmacology of Da-Cheng-Qi decoction in experimental acute pancreatitis in rats. Evid Based Complement Alternat Med, 2015, 2015: 283175.
14.	吳建新, 袁耀宗, 徐家裕. 大鼠急性壞死型胰腺炎病理特征評定方法的研究. 中國實驗動物學報, 2002, 10(4): 210-213.
15.	Liu N, Wan Y, Tong Y, et al. A clinic-radiomics model for predicting the incidence of persistent organ failure in patients with acute necrotizing pancreatitis. Gastroenterol Res Pract, 2023, 2023: 2831024.
16.	Diéguez-Castillo C, Jiménez-Luna C, Martín-Ruiz JL, et al. Role of exocrine and endocrine insufficiency in the management of patients with chronic pancreatitis. J Clin Med, 2020, 9(6): 2014.
17.	Harindranath S, Patra BR, Ansari AA, et al. Ductal intervention in chronic pancreatitis: impact on glycemic control and endocrine insufficiency management. Cureus, 2024, 16(8): e66378.
18.	Merkord J, Jonas L, Weber H, et al. Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): pathogenesis and natural course of lesions. Pancreas, 1997, 15(4): 392-401.
19.	Lampel M, Kern HF. Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch A Pathol Anat Histol, 1977, 373(2): 97-117.
20.	Matsumura N, Ochi K, Ichimura M, et al. Study on free radicals and pancreatic fibrosis--pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor. Pancreas, 2001, 22(1): 53-57.
21.	Puig-Diví V, Molero X, Salas A, et al. Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Pancreas, 1996, 13(4): 417-424.
22.	Le T, Eisses JF, Lemon KL, et al. Intraductal infusion of taurocholate followed by distal common bile duct ligation leads to a severe necrotic model of pancreatitis in mice. Pancreas, 2015, 44(3): 493-499.
23.	Runkel NS, Smith GS, Rodriguez LF, et al. Influence of shock on development of infection during acute pancreatitis in the rat. Dig Dis Sci, 1992, 37(9): 1418-1425.
24.	Yao JQ, Zhu L, Miao YF, et al. Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis. World J Gastroenterol, 2020, 26(22): 3056-3075.
25.	Saugel B, Umgelter A, Martin F, et al. Systemic capillary leak syndrome associated with hypovolemic shock and compartment syndrome. Use of transpulmonary thermodilution technique for volume management. Scand J Trauma Resusc Emerg Med, 2010, 18: 38.
26.	Lakananurak N, Gramlich L. Nutrition management in acute pancreatitis: clinical practice consideration. World J Clin Cases, 2020, 8(9): 1561-1573.
27.	Thomas T, Mah L, Barreto SG. Systematic review of diet in the pathogenesis of acute pancreatitis: a tale of too much or too little?. Saudi J Gastroenterol, 2012, 18(5): 310-315.
28.	Daftary A, Acton J, Heubi J, et al. Fecal elastase-1: utility in pancreatic function in cystic fibrosis. J Cyst Fibros, 2006, 5(2): 71-76.
29.	Walkowiak J, Herzig KH, Strzykala K, et al. Fecal elastase-1 is superior to fecal chymotrypsin in the assessment of pancreatic involvement in cystic fibrosis. Pediatrics, 2002, 110(1 Pt 1): e7.
30.	Ouyang D, Dhall D, Yu R. Pathologic pancreatic endocrine cell hyperplasia. World J Gastroenterol, 2011, 17(2): 137-143.

1. Beger HG, Rau BM. Severe acute pancreatitis: clinical course and management. World J Gastroenterol, 2007, 13(38): 5043-5051.
2. Italian Association for the Study of the Pancreas (AISP), Pezzilli R, Zerbi A, et al. Consensus guidelines on severe acute pancreatitis. Dig Liver Dis, 2015, 47(7): 532-543.
3. 姚佳心, 黃會芳, 付澤花. 腫塊型慢性胰腺炎與胰腺癌的鑒別診斷. 胃腸病學和肝病學雜志, 2025, 34(1): 148-153.
4. Rasmussen HH, Irtun O, Olesen SS, et al. Nutrition in chronic pancreatitis. World J Gastroenterol, 2013, 19(42): 7267-7275.
5. Chowdhury RS, Forsmark CE. Review article: pancreatic function testing. Aliment Pharmacol Ther, 2003, 17(6): 733-750.
6. Hollemans RA, Hallensleben NDL, Mager DJ, et al. Pancreatic exocrine insufficiency following acute pancreatitis: systematic review and study level meta-analysis. Pancreatology, 2018, 18(3): 253-262.
7. Wu D, Xu Y, Zeng Y, et al. Endocrine pancreatic function changes after acute pancreatitis. Pancreas, 2011, 40(7): 1006-1011.
8. Hamada S, Matsumoto R, Masamune A. Pancreatic stellate cells and metabolic alteration: physiology and pathophysiology. Front Physiol, 2022, 13: 865105.
9. Fonseca Sepúlveda EV, Guerrero-Lozano R. Acute pancreatitis and recurrent acute pancreatitis: an exploration of clinical and etiologic factors and outcomes. J Pediatr (Rio J), 2019, 95(6): 713-719.
10. Balint ER, Fur G, Kiss L, et al. Assessment of the course of acute pancreatitis in the light of aetiology: a systematic review and meta-analysis. Sci Rep, 2020, 10(1): 17936.
11. Su YR, Hong YP, Mei FC, et al. High-fat diet aggravates the intestinal barrier injury via TLR4-RIP3 pathway in a rat model of severe acute pancreatitis. Mediators Inflamm, 2019, 2019: 2512687.
12. Hu J, Zhang YM, Miao YF, et al. Effects of Yue-Bi-Tang on water metabolism in severe acute pancreatitis rats with acute lung-kidney injury. World J Gastroenterol, 2020, 26(43): 6810-6821.
13. Zhao X, Zhang Y, Li J, et al. Tissue pharmacology of Da-Cheng-Qi decoction in experimental acute pancreatitis in rats. Evid Based Complement Alternat Med, 2015, 2015: 283175.
14. 吳建新, 袁耀宗, 徐家裕. 大鼠急性壞死型胰腺炎病理特征評定方法的研究. 中國實驗動物學報, 2002, 10(4): 210-213.
15. Liu N, Wan Y, Tong Y, et al. A clinic-radiomics model for predicting the incidence of persistent organ failure in patients with acute necrotizing pancreatitis. Gastroenterol Res Pract, 2023, 2023: 2831024.
16. Diéguez-Castillo C, Jiménez-Luna C, Martín-Ruiz JL, et al. Role of exocrine and endocrine insufficiency in the management of patients with chronic pancreatitis. J Clin Med, 2020, 9(6): 2014.
17. Harindranath S, Patra BR, Ansari AA, et al. Ductal intervention in chronic pancreatitis: impact on glycemic control and endocrine insufficiency management. Cureus, 2024, 16(8): e66378.
18. Merkord J, Jonas L, Weber H, et al. Acute interstitial pancreatitis in rats induced by dibutyltin dichloride (DBTC): pathogenesis and natural course of lesions. Pancreas, 1997, 15(4): 392-401.
19. Lampel M, Kern HF. Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch A Pathol Anat Histol, 1977, 373(2): 97-117.
20. Matsumura N, Ochi K, Ichimura M, et al. Study on free radicals and pancreatic fibrosis--pancreatic fibrosis induced by repeated injections of superoxide dismutase inhibitor. Pancreas, 2001, 22(1): 53-57.
21. Puig-Diví V, Molero X, Salas A, et al. Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts. Pancreas, 1996, 13(4): 417-424.
22. Le T, Eisses JF, Lemon KL, et al. Intraductal infusion of taurocholate followed by distal common bile duct ligation leads to a severe necrotic model of pancreatitis in mice. Pancreas, 2015, 44(3): 493-499.
23. Runkel NS, Smith GS, Rodriguez LF, et al. Influence of shock on development of infection during acute pancreatitis in the rat. Dig Dis Sci, 1992, 37(9): 1418-1425.
24. Yao JQ, Zhu L, Miao YF, et al. Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis. World J Gastroenterol, 2020, 26(22): 3056-3075.
25. Saugel B, Umgelter A, Martin F, et al. Systemic capillary leak syndrome associated with hypovolemic shock and compartment syndrome. Use of transpulmonary thermodilution technique for volume management. Scand J Trauma Resusc Emerg Med, 2010, 18: 38.
26. Lakananurak N, Gramlich L. Nutrition management in acute pancreatitis: clinical practice consideration. World J Clin Cases, 2020, 8(9): 1561-1573.
27. Thomas T, Mah L, Barreto SG. Systematic review of diet in the pathogenesis of acute pancreatitis: a tale of too much or too little?. Saudi J Gastroenterol, 2012, 18(5): 310-315.
28. Daftary A, Acton J, Heubi J, et al. Fecal elastase-1: utility in pancreatic function in cystic fibrosis. J Cyst Fibros, 2006, 5(2): 71-76.
29. Walkowiak J, Herzig KH, Strzykala K, et al. Fecal elastase-1 is superior to fecal chymotrypsin in the assessment of pancreatic involvement in cystic fibrosis. Pediatrics, 2002, 110(1 Pt 1): e7.
30. Ouyang D, Dhall D, Yu R. Pathologic pancreatic endocrine cell hyperplasia. World J Gastroenterol, 2011, 17(2): 137-143.

West China Medical Journal

A modeling method for establishing an experimental animal model of digestive dysfunction in the late stage of severe acute pancreatitis

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