动物肠缺氧模型研究进展

doi:10.11843/j.issn.0366-6964.2023.10.008

Abstract

Abstract: Intestinal hypoxia is a pathological phenomenon in which the oxygen demand of intestinal tissues is higher than the oxygen supply. It is one of the direct triggers, early warning signals and key features of various intestinal diseases. The establishment of real and reliable animal models of intestinal hypoxia or cellular models that can simulate intestinal hypoxia is essential for the study of the pathological mechanisms of intestinal hypoxia-related diseases. The methods applicable to the construction of intestinal hypoxia models in recent years are reviewed in this paper, Focused on the construction strategies, advantages and disadvantages, and application scenarios of models including circulatory, chemical and environmental animal models of intestinal hypoxia, physically and chemically induced cellular models of intestinal hypoxia in vitro, as well as isolated intestinal organoid models of hypoxia in vitro, in the hope of providing reference for the study of the pathogenesis of intestinal hypoxia diseases in animals and the discovery and clinical pharmacodynamic evaluation of therapeutic drugs.

Key words: intestinal hypoxia, cellular models, animal models, intestinal organoids

CLC Number:

S858

DAI Wen, BIAN Sushu, ZHANG Jumin, SONG Houhui, ZHOU Yingshan, LIU Ping, WANG Xiaodu. Research Progress of Intestinal Hypoxia Models in Animals[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(10): 4083-4094.

References 89

[1]	COLGAN S P, TAYLOR C T.Hypoxia:an alarm signal during intestinal inflammation[J].Nat Rev Gastroenterol Hepatol, 2010, 7(5):281-287.
[2]	ELTZSCHIG H K, ECKLE T.Ischemia and reperfusion-from mechanism to translation[J].Nat Med, 2011, 17(11):1391-1401.
[3]	马殿伟, 谢学军, 李晓微.缺氧实验模型研究进展[J].医学综述, 2007, 13(23):1795-1798.MA D W, XIE X J, LI X W.Research development of experimental model with hypoxia[J].Medical Recapitulate, 2007, 13(23):1795-1798.(in Chinese)
[4]	TAYLOR C T, COLGAN S P.Regulation of immunity and inflammation by hypoxia in immunological niches[J].Nat Rev Immunol, 2017, 17(12):774-785.
[5]	VAN WELDEN S, SELFRIDGE A C, HINDRYCKX P.Intestinal hypoxia and hypoxia-induced signalling as therapeutic targets for IBD[J].Nat Rev Gastroenterol Hepatol, 2017, 14(10):596-611.
[6]	ROBRAHN L, JIAO L, CRAMER T.Barrier integrity and chronic inflammation mediated by HIF-1 impact on intestinal tumorigenesis[J].Cancer Lett, 2020, 490:186-192.
[7]	TAYLOR C T, COLGAN S P.Hypoxia and gastrointestinal disease[J].J Mol Med (Berl), 2007, 85(12):1295-1300.
[8]	PRAL L P, FACHI J L, CORRÊA R O, et al.Hypoxia and HIF-1 as key regulators of gut microbiota and host interactions[J].Trends Immunol, 2021, 42(7):604-621.
[9]	温爽.复方中药对腹水综合征肉鸡空肠紧密连接和炎症因子的影响[D].晋中:山西农业大学, 2019.WEN S.Effect of compound traditional Chinese medicine on jejunum tight junction and inflammatory factors in broilers with Ascitic Syndrome[D].Jinzhong:Shanxi Agricultural University, 2019.(in Chinese)
[10]	GLOVER L E, LEE J S, COLGAN S P.Oxygen metabolism and barrier regulation in the intestinal mucosa[J].J Clin Invest, 2016, 126(10):3680-3688.
[11]	陆逸, 蔡杰, 王迪铭, 等.动物低氧应激与线粒体功能机制[J].动物营养学报, 2020, 32(11):5046-5052.LU Y, CAI J, WANG D M, et al.Hypoxic stress and mitochondrial function mechanism in animals[J].Chinese Journal of Animal Nutrition, 2020, 32(11):5046-5052.(in Chinese)
[12]	GRANGER D N, HOLM L, KVIETYS P.The gastrointestinal circulation:physiology and pathophysiology[J].Compr Physiol, 2015, 5(3):1541-1583.
[13]	杨硕菲, 吴性江.缺氧诱导因子在肠缺氧中的研究进展[J].肠外与肠内营养, 2015, 22(5):307-311.YANG S F, WU X J.Research advancement of hypoxia-inducible factor in intestinal hypoxia[J].Parenteral & Enteral Nutrition, 2015, 22(5):307-311.(in Chinese)
[14]	WAN Z Q, ZHANG X F, JIA X H, et al.Lactobacillus johnsonii YH1136 plays a protective role against endogenous pathogenic bacteria induced intestinal dysfunction by reconstructing gut microbiota in mice exposed at high altitude[J].Front Immunol, 2022, 13:1007737.
[15]	GONZALEZ L M, MOESER A J, BLIKSLAGER A T.Animal models of ischemia-reperfusion-induced intestinal injury:progress and promise for translational research[J].Am J Physiol Gastrointest Liver Physiol, 2015, 308(2):G63-G75.
[16]	DENG F, HU J J, YANG X, et al.Gut microbial metabolite pravastatin attenuates intestinal ischemia/reperfusion injury through promoting IL-33 release from type Ⅱ innate lymphoid cells via IL-33/ST2 signaling[J].Front Immunol, 2021, 12:704836.
[17]	GUO J F, LOU X K, GONG W Y, et al.The effects of different stress on intestinal mucosal barrier and intestinal microecology were discussed based on three typical animal models[J].Front Cell Infect Microbiol, 2022, 12:953474.
[18]	DENG F, LIN Z B, SUN Q S, et al.The role of intestinal microbiota and its metabolites in intestinal and extraintestinal organ injury induced by intestinal ischemia reperfusion injury[J].Int J Biol Sci, 2022, 18(10):3981-3992.
[19]	DENG F, ZHAO B C, YANG X, et al.The gut microbiota metabolite capsiate promotes Gpx4 expression by activating TRPV1 to inhibit intestinal ischemia reperfusion-induced ferroptosis[J].Gut Microbes, 2021, 13(1):1902719.
[20]	TIAN Y, SHU R, LEI Y, et al.Somatostatin attenuates intestinal epithelial barrier injury during acute intestinal ischemia-reperfusion through Tollip/Myeloiddifferentiationfactor 88/Nuclear factor kappa-B signaling[J].Bioengineered, 2022, 13(3):5005-5020.
[21]	MURTHY S, QING H Q, SAKAI T, et al.Ischemia/reperfusion injury in the rat colon[J].Inflammation, 1997, 21(2):173-190.
[22]	JI A L, LI T, ZU G, et al.Ubiquitin-specific protease 22 enhances intestinal cell proliferation and tissue regeneration after intestinal ischemia reperfusion injury[J].World J Gastroenterol, 2019, 25(7):824-836.
[23]	GAO Y F, ZHANG H J, WANG Y J, et al.L-cysteine alleviates myenteric neuron injury induced by intestinal ischemia/reperfusion via inhibitin the macrophage NLRP3-IL-1β pathway[J].Front Pharmacol, 2022, 13:899169.
[24]	LIU C L, DING R W, HUANG W J, et al.Sevoflurane protects against intestinal ischemia-reperfusion injury by activating peroxisome proliferator-activated receptor gamma/nuclear factor-κB pathway in rats[J].Pharmacology, 2020, 105(3-4):231-242.
[25]	PARLAR A, ARSLAN S O.Resveratrol normalizes the deterioration of smooth muscle contractility after intestinal ischemia and reperfusion in rats associated with an antioxidative effect and modulating tumor necrosis factor alpha activity[J].Ann Vasc Surg, 2019, 61:416-426.
[26]	LIU C L, SHEN Z W, LIU Y H, et al.Sevoflurane protects against intestinal ischemia-reperfusion injury partly by phosphatidylinositol 3 kinases/Akt pathway in rats[J].Surgery, 2015, 157(5):924-933.
[27]	TURAN I, OZACMAK H S, OZACMAK V H, et al.Agmatine attenuates intestinal ischemia and reperfusion injury by reducing oxidative stress and inflammatory reaction in rats[J].Life Sci, 2017, 189:23-28.
[28]	SAYHAN M B, OGUZ S, SALT Ö, et al.Sesamin ameliorates mucosal tissue injury of mesenteric ischemia and reperfusion in an experimental rat model[J].Arch Med Sci, 2019, 15(6):1582-1588.
[29]	ANSARI F A, KHAN A A, MAHMOOD R.Protective effect of carnosine and N-acetylcysteine against sodium nitrite-induced oxidative stress and DNA damage in rat intestine[J].Environ Sci Pollut Res Int, 2018, 25(20):19380-19392.
[30]	KHATUN F, AIZU Y, NISHIDATE I.Transcutaneous monitoring of hemoglobin derivatives during methemoglobinemia in rats using spectral diffuse reflectance[J].J Biomed Opt, 2021, 26(3):033708.
[31]	BAI X, LIU G Q, YANG J X, et al.Changes in the gut microbiota of rats in high-altitude hypoxic environments[J].Microbiol Spectr, 2022, 10(6):e01626-22.
[32]	罗涵.TLR4/NF-κB在低氧暴露下大鼠肠道屏障功能损伤及细菌移位中的作用研究[D].重庆:第三军医大学, 2013.LUO H.Role of TLR4/NF-κB in damage to intestinal mucosa barrier function and bacterial translocation in rats exposed to hypoxia[D].Chongqing:Third Military Medical University, 2013.(in Chinese)
[33]	JI Q R, ZHANG Y, ZHOU Y L, et al.Effects of hypoxic exposure on immune responses of intestinal mucosa to Citrobacter colitis in mice[J].Biomed Pharmacother, 2020, 129:110477.
[34]	赫玉宝.模拟急进高原缺氧对大鼠肠黏膜的损伤及缺氧相关蛋白的影响[D].兰州:甘肃中医药大学, 2018.HE Y B.Effect of simulated acute plateau hypoxia on intestinal mucosa injury and hypoxia-related protein in rats[D].Lanzhou:Gansu University of Chinese Medicine, 2018.(in Chinese)
[35]	YIN L H, GAO M, XU L N, et al.Single-cell analysis of cellular heterogeneity and interactions in the ischemia-reperfusion injured mouse intestine[J/OL].J Pharm Anal, 2023[2022-11-11]..https://www.sciencedirect.com/science/article/pii/S2095177923000059.
[36]	DAI D, DAI F D, CHEN J C, et al.Integrated multi-omics reveal important roles of gut contents in intestinal ischemia-reperfusion induced injuries in rats[J].Commun Biol, 2022, 5(1):938.
[37]	AHMED M.Ischemic bowel disease in 2021[J].World J Gastroenterol, 2021, 27(29):4746-4762.
[38]	余鸿, 吴雨岭, 韩艺, 等.缺氧条件下鼠胚软骨c-Fos和巢蛋白表达及当归的保护作用[J].中国临床康复, 2006, 10(11):111-113.YU H, WU Y L, HAN Y, et al.Effect of Chinese angelica on the expression of c-Fos and nidogen in embryonic cartilage of rats during hypoxia stage[J].Chinese Journal of Clinical Rehabilitation, 2006, 10(11):111-113.(in Chinese)
[39]	CHENG J F, SUN Y M, HE J X, et al.The mechanism of colon tissue damage mediated by HIF-1α/NF-κB/STAT1 in high-altitude environment[J].Front Physiol, 2022, 13:933659.
[40]	王黎, 史清海, 胡科妍, 等.优化及复氧对急进高原缺氧大鼠认知功能障碍的改善作用[J].华南国防医学杂志, 2018, 32(1):5-7, 41.WANG L, SHI Q H, HU K Y, et al.Improvement of optimization and reoxygenation on cognitive dysfunction in plateau hypoxia rats[J].Military Medical Journal of South China, 2018, 32(1):5-7, 41.(in Chinese)
[41]	BURTSCHER J, MALLET R T, BURTSCHER M, et al.Hypoxia and brain aging:neurodegeneration or neuroprotection?[J].Ageing Res Rev, 2021, 68:101343.
[42]	RIECH S, KALLENBERG K, MOERER O, et al.The pattern of brain microhemorrhages after severe lung failure resembles the one seen in high-altitude cerebral edema[J].Crit Care Med, 2015, 43(9):e386-e389.
[43]	李龙, 刘锁珠, 王宏辉, 等.益生菌对高海拔缺氧条件下肉鸡生产性能和肠道功能的影响[J].家畜生态学报, 2018, 39(7):25-29.LI L, LIU S Z, WANG H H, et al.Effects of probiotics on growth performance and intestine function of broiler reared at hypoxic environment in high altitude[J].Acta Ecologiae Animalis Domastici, 2018, 39(7):25-29.(in Chinese)
[44]	滕文彬, 李玉红, 祝胜美.低氧诱导因子的调控途径和在肠道疾病中的作用[J].中国病理生理杂志, 2019, 35(10):1894-1900.TENG W B, LI Y H, ZHU S M.Regulatory pathway of hypoxia-inducible factor and its role in intestinal diseases[J].Chinese Journal of Pathophysiology, 2019, 35(10):1894-1900.(in Chinese)
[45]	马雪, 史清海.缺氧动物及细胞实验模型的研究进展[J].西北国防医学杂志, 2016, 37(8):535-538.MA X, SHI Q H.Research progress of hypoxic animal and cell experimental models[J].Medical Journal of National Defending Forces in Northwest China, 2016, 37(8):535-538.(in Chinese)
[46]	杨松巍.NF-κB/HIF-1α通路在IFN-γ诱导的肠上皮屏障损害中的机制研究[D].重庆:第三军医大学, 2014.YANG S W.NF-κB/HIF-1α pathway involved in IFN-γ induced intestinal epithelial barrier disfunction[D].Chongqing:Third Military Medical University, 2014.(in Chinese)
[47]	王彬彬.模拟高原缺氧大鼠肠上皮细胞损伤自噬调控机制的研究[D].兰州:甘肃中医药大学, 2016.WANG B B.Research mechanism of autophagy in rat intestinal epithelial cells injury induced by simulated altitude hypoxia[D].Lanzhou:Gansu University of Chinese Medicine, 2016.(in Chinese)
[48]	GAO H N, REN F Z, WEN P C, et al.Yak milk-derived exosomal microRNAs regulate intestinal epithelial cells on proliferation in hypoxic environment[J].J Dairy Sci, 2021, 104(2):1291-1303.
[49]	张秀杨, 张龙飞, 陈世远, 等.缺氧诱导因子1α介导单羧酸转运蛋白1表达参与短链脂肪酸对肠道缺氧保护作用的研究[J].中华普通外科学文献, 2023, 17(1):18-23.ZHANG X Y, ZHANG L F, CHEN S Y, et al.Hypoxia-inducible factor-1α mediating the expression of monocarboxylate transporter-1 and participating in the protective effect of short-chain fatty acids on intestinal hypoxia[J].Chinese Archives of General Surgery (Electronic Edition), 2023, 17(1):18-23.(in Chinese)
[50]	MUENCHAU S, DEUTSCH R, DE CASTRO I J, et al.Hypoxic environment promotes barrier formation in human intestinal epithelial cells through regulation of microRNA 320a expression[J].Mol Cell Biol, 2019, 39(14):e00553-18.
[51]	LI Y, FENG D C, WANG Z Y, et al.Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion[J].Cell Death Differ, 2019, 26(11):2284-2299.
[52]	FACHI J L, PRAL L P, DOS SANTOS J A C, et al.Hypoxia enhances ILC3 responses through HIF-1α-dependent mechanism[J].Mucosal Immunol, 2021, 14(4):828-841.
[53]	XIE L W, COLLINS J F.Transcription factors Sp1 and Hif2α mediate induction of the copper-transporting ATPase (Atp7a) gene in intestinal epithelial cells during hypoxia[J].J Biol Chem, 2013, 288(33):23943-23952.
[54]	罗红敏.丙戊酸钠对严重烫伤后肠屏障功能的保护作用及机制研究[D].北京:中国人民解放军医学院, 2014.LUO H M.The protective effects of valproic acid on gut barrier function after major burn injury and its underlying mechanisms[D].Beijing:People's Liberation Army Medical College, 2014.(in Chinese)
[55]	BASAVARAJU A M, SHIVANNA N, YADAVALLI C, et al.Ameliorative effect of Ananas comosus on cobalt chloride-induced hypoxia in Caco2 cells via HIF-1α, GLUT 1, VEGF, ANG and FGF[J].Biol Trace Elem Res, 2021, 199(4):1345-1355.
[56]	BONCLER M, LUKASIAK M, DASTYCH J, et al.Differentiated mitochondrial function in mouse 3T3 fibroblasts and human epithelial or endothelial cells in response to chemical exposure[J].Basic Clin Pharmacol Toxicol, 2019, 124(2):199-210.
[57]	DIGUILIO K M, VALENZANO M C, RYBAKOVSKY E, et al.Cobalt chloride compromises transepithelial barrier properties of CaCo-2 BBe human gastrointestinal epithelial cell layers[J].BMC Gastroenterol, 2018, 18(1):2.
[58]	LIU Y L, WANG C H, WANG Y H, et al.Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells[J].Toxicol Appl Pharmacol, 2012, 264(2):212-221.
[59]	DONG B L, SONG W H, KONG X Q, et al.Visualizing cellular sodium hydrosulfite (Na2S2O4) using azo-based fluorescent probes with a high signal-to-noise ratio[J].J Mater Chem B, 2019, 7(5):730-733.
[60]	TIAN Y, LI Y F, WANG W X, et al.Novel strategy for validating the existence and mechanism of the "Gut-Liver Axis" in vivo by a hypoxia-sensitive NIR fluorescent probe[J].Anal Chem, 2020, 92(6):4244-4250.
[61]	KHONG T L, THAIRU N, LARSEN H, et al.Identification of the angiogenic gene signature induced by EGF and hypoxia in colorectal cancer[J].BMC Cancer, 2013, 13:518.
[62]	CUMMINS E P, SEEBALLUCK F, KEELY S J, et al.The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis[J].Gastroenterology, 2008, 134(1):156-165.e1.
[63]	DENGLER F, GÄBEL G.The fast lane of hypoxic adaptation:Glucose transport is modulated via a HIF-hydroxylase-AMPK-axis in jejunum epithelium[J].Int J Mol Sci, 2019, 20(20):4993.
[64]	ZEITOUNI N E, DERSCH P, NAIM H Y, et al.Hypoxia decreases invasin-mediated Yersinia enterocolitica internalization into Caco-2 cells[J].PLoS One, 2016, 11(1):e0146103.
[65]	KAMIYA T, KOWN A H, KANEMAKI T, et al.A simplified model of hypoxic injury in primary cultured rat hepatocytes[J].In Vitro Cell Dev Biol Anim, 1998, 34(2):131-137.
[66]	MUÑOZ-SÁNCHEZ J, CHÁNEZ-CÁRDENAS M E.The use of cobalt chloride as a chemical hypoxia model[J].J Appl Toxicol, 2019, 39(4):556-570.
[67]	许蜀闽, 王培勇, 马红英.连二亚硫酸钠在建立培养细胞的无氧环境中的应用[J].第三军医大学学报, 2005, 27(4):359-360.XU S M, WANG P Y, MA H Y.Preparation of hypoxic surroundings with sodium dihionite for cell culture[J].Acta Academiae Medicinae Militaris Tertiae, 2005, 27(4):359-360.(in Chinese)
[68]	SWEET R, PAUL A, ZASTRE J.Hypoxia induced upregulation and function of the thiamine transporter, SLC19A3 in a breast cancer cell line[J].Cancer Biol Ther, 2010, 10(11):1101-1111.
[69]	SABUI S, RAMAMOORTHY K, ROMERO J M, et al.Hypoxia inhibits colonic uptake of the microbiota-generated forms of vitamin B1 via HIF-1α-mediated transcriptional regulation of their transporters[J].J Biol Chem, 2022, 298(2):101562.
[70]	王修启, 谢文文, 周加义.农业动物肠道类器官研究进展[J].饲料工业, 2022, 43(18):1-7.WANG X Q, XIE W W, ZHOU J Y.Recent advances in intestinal organoids of farm animals[J].Feed Industry, 2022, 43(18):1-7.(in Chinese)
[71]	ZUR BRUEGGE T F, LIESE A, DONATH S, et al.Intestinal organoids in colitis research:focusing on variability and cryopreservation[J].Stem Cells Int, 2021, 2021:9041423.
[72]	BURCLAFF J, BLITON R J, BREAU K A, et al.A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics[J].Cell Mol Gastroenterol Hepatol, 2022, 13(5):1554-1589.
[73]	WÖRSDÖRFER P, ERGVN S.The impact of oxygen availability and multilineage communication on organoid maturation[J].Antioxid Redox Signal, 2021, 35(3):217-233.
[74]	ZHAO D, FARNELL M B, KOGUT M H, et al.From crypts to enteroids:establishment and characterization of avian intestinal organoids[J].Poult Sci, 2022, 101(3):101642.
[75]	HILL D R, HUANG S, NAGY M S, et al.Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium[J].eLife, 2017, 6:e29132.
[76]	KIP A M, SOONS Z, MOHREN R, et al.Proteomics analysis of human intestinal organoids during hypoxia and reoxygenation as a model to study ischemia-reperfusion injury[J].Cell Death Dis, 2021, 12(1):95.
[77]	KIP A M, GROOTJANS J, MANCA M, et al.Temporal transcript profiling identifies a role for unfolded protein stress in human gut ischemia-reperfusion injury[J].Cell Mol Gastroenterol Hepatol, 2022, 13(3):681-694.
[78]	DE LANGE I H, VAN GORP C, MASSY K R I, et al.Hypoxia-driven changes in a human intestinal organoid model and the protective effects of hydrolyzed whey[J].Nutrients, 2023, 15(2):393.
[79]	KOIKE Y, LI B, LEE C, et al.The intestinal injury caused by ischemia-reperfusion is attenuated by amniotic fluid stem cells via the release of tumor necrosis factor-stimulated gene 6 protein[J].FASEB J, 2020, 34(5):6824-6836.
[80]	WALAAS G A, GOPALAKRISHNAN S, BAKKE I, et al.Physiological hypoxia improves growth and functional differentiation of human intestinal epithelial organoids[J].Front Immunol, 2023, 14:1095812.
[81]	ALLWOOD M A, EDGETT B A, EADIE A L, et al.Moderate and severe hypoxia elicit divergent effects on cardiovascular function and physiological rhythms[M].J Physiol, 2018, 596(15):3391-3410.
[82]	王艺博, 王峰, 肖智勇, 等.大株红景天胶囊提高小鼠耐常压缺氧能力和抗疲劳作用[J].中国药理学与毒理学杂志, 2021, 35(6):420-426.WANG Y B, WANG F, XIAO Z Y, et al.Large plant Rhodiola capsules improve normobaric hypoxia tolerance and anti-fatigue action in mice[J].Chinese Journal of Pharmacology and Toxicology, 2021, 35(6):420-426.(in Chinese)
[83]	董晓敏, 孙笑语, 童学红, 等.机能学实验中常压与低压缺氧环境下小鼠耐受性的比较[J].继续医学教育, 2018, 32(12):72-73.DONG X M, SUN X Y, TONG X H, et al.Comparison of tolerance between hypobaric hypoxia and normobaric hypoxia in medical functional teaching experiment[J].Continuing Medical Education, 2018, 32(12):72-73.(in Chinese)
[84]	MORRIS N L, CANNON A R, LI X L, et al.Protective effects of PX478 on gut barrier in a mouse model of ethanol and burn injury[J].J Leukoc Biol, 2021, 109(6):1121-1130.
[85]	CHOUDHRY M A, BA Z F, RANA S N, et al.Alcohol ingestion before burn injury decreases splanchnic blood flow and oxygen delivery[J].Am J Physiol Heart Circ Physiol, 2005, 288(2):H716-H721.
[86]	WALLIN D J, TKAC I, STUCKER S, et al.Phlebotomy-induced anemia alters hippocampal neurochemistry in neonatal mice[J].Pediatr Res, 2015, 77(6):765-771.
[87]	ARTHUR C M, NALBANT D, FELDMAN H A, et al.Anemia induces gut inflammation and injury in an animal model of preterm infants[J].Transfusion, 2019, 59(4):1233-1245.
[88]	BALLS M.It's time to reconsider the principles of humane experimental technique[J].Altern Lab Anim, 2020, 48(1):40-46.
[89]	BEAUMONT M, BLANC F, CHERBUY C, et al.Intestinal organoids in farm animals[J].Vet Res, 2021, 52(1):33.

Research Progress of Intestinal Hypoxia Models in Animals

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