{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T14:17:34Z","timestamp":1768745854608,"version":"3.49.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>The present study aimed to determine the effect of aerobic exercise on improving damage to intestinal mucosal barrier function caused by obstructive jaundice (OJ) and explore the mechanism. Fifty male KM mice were divided into five groups: sham operation group (S), model group (M), exercise group (TM), DL-propargylglycine + exercise (PT) group, and sodium hydrosulfide + exercise (NT) group. Additionally, mice in S group underwent common bile duct ligation for 48 h to establish a murine obstructive jaundice model. In PT group, propargylglycine (40 mg\/kg) was intraperitoneally injected 7 days after surgery. NaHS (50 \u03bcmol\/kg) was intraperitoneally injected into mice in the NT group 7 days after surgery. The TM group, NT group and PT group exercised on a slope of 0% at a speed of 10 m\/min without weight training (30 min\/day). HE staining showed that the intestinal mucosa of group M was atrophied and that the villi were broken. The intestinal mucosal structure of mice in the TM group was improved. Serum assays showed that H<jats:sub>2<\/jats:sub>S levels were higher in the TM group than in the M group; compared with the levels in the TM group, the PT group levels were decreased and the NT group levels were increased. In addition, aerobic exercise inhibits the HMGB1\/TLR4\/NF-\u03baB signaling pathway by promoting endogenous H<jats:sub>2<\/jats:sub>S production, thereby exerting a protective effect on the intestinal mucosal barrier.<\/jats:p>","DOI":"10.3389\/fphys.2021.732780","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T06:50:12Z","timestamp":1643957412000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Physical Exercise Repairs Obstructive Jaundice-Induced Damage to Intestinal Mucosal Barrier Function via H2S-Mediated Regulation of the HMGB1\/Toll Like Receptors 4\/Nuclear Factor Kappa B Pathway"],"prefix":"10.3389","volume":"12","author":[{"given":"Changfeng","family":"Shao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaqin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afang","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1136\/gutjnl-2011-300776","article-title":"A novel myokine, secreted protein acidic and rich in cysteine (SPARC), suppresses colon tumorigenesis via regular exercise.","volume":"62","author":"Aoi","year":"2013","journal-title":"Gut"},{"key":"B2","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.jss.2016.07.020","article-title":"Murine model of long-term obstructive jaundice.","volume":"206","author":"Aoki","year":"2016","journal-title":"J. Surg. Res."},{"key":"B3","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.cellsig.2004.08.005","article-title":"Involvement of PKC\u03b1\/\u03b2 in TLR4 and TLR2 dependent activation of NF-\u03baB.","volume":"17","author":"Asehnoune","year":"2005","journal-title":"Cell. Signal."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/mi.2016.9","article-title":"Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation.","volume":"9","author":"Banerjee","year":"2016","journal-title":"Mucosal Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.nut.2018.09.019","article-title":"Nutrients, immune system, and exercise: where will it take us?","volume":"61","author":"Batatinha","year":"","journal-title":"Nutrition"},{"key":"B6","doi-asserted-by":"publisher","first-page":"14883","DOI":"10.1002\/jcp.28318","article-title":"Regulation of autophagy as a therapy for immunosenescence-driven cancer and neurodegenerative diseases: the role of exercise.","volume":"234","author":"Batatinha","year":"","journal-title":"J. Cell. Physiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1600-065X.2007.00574.x","article-title":"High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity.","volume":"220","author":"Bianchi","year":"2007","journal-title":"Immunol. Rev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/ars.2017.7058","article-title":"A review of hydrogen sulfide synthesis, metabolism, and measurement: is modulation of hydrogen sulfide a novel therapeutic for cancer?","volume":"31","author":"Cao","year":"2018","journal-title":"Antioxid. Redox Signal."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-07094-y","article-title":"Blockade of high-mobility group box 1 attenuates intestinal mucosal barrier dysfunction in experimental acute pancreatitis.","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"B10","doi-asserted-by":"publisher","first-page":"199","DOI":"10.20524\/aog.2019.0358","article-title":"Comparison of digital versus fiberoptic cholangioscopy in patients requiring evaluation of bile duct disease or treatment of biliary stones.","volume":"32","author":"Dimas","year":"2019","journal-title":"Ann. Gastroenterol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/nri3041","article-title":"The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease.","volume":"11","author":"Gleeson","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1845","DOI":"10.1002\/oby.21170","article-title":"Exercise improves adipose function and inflammation and ameliorates fatty liver disease in obese diabetic mice.","volume":"23","author":"Haczeyni","year":"2015","journal-title":"Obesity"},{"key":"B13","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.fsi.2020.01.006","article-title":"Ghrelin modulates the immune response and increases resistance to Aeromonas hydrophila infection in hybrid tilapia.","volume":"98","author":"Han","year":"2020","journal-title":"Fish Shellfish Immunol."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078350","article-title":"Sedentary time and markers of chronic low-grade inflammation in a high risk population.","volume":"8","author":"Henson","year":"2013","journal-title":"PLoS One"},{"key":"B15","doi-asserted-by":"publisher","first-page":"295","DOI":"10.3892\/br.2020.1299","article-title":"Diet induces hepatocyte protection in fatty liver disease via modulation of PTEN signaling (Review).","volume":"12","author":"Ikeda","year":"2020","journal-title":"Biomed. Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.amjsurg.2006.07.015","article-title":"Selective versus total biliary drainage for obstructive jaundice caused by a hepatobiliary malignancy.","volume":"193","author":"Ishizawa","year":"2007","journal-title":"Am. J. Surg."},{"key":"B17","doi-asserted-by":"publisher","first-page":"342","DOI":"10.21037\/hbsn.2019.10.27","article-title":"Nutritional support treatment for perioperative patients in hepatobiliary surgery.","volume":"9","author":"Jin","year":"2019","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1136\/gut.46.5.725","article-title":"Endotoxin, cytokines, and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage.","volume":"46","author":"Kimmings","year":"2000","journal-title":"Gut"},{"key":"B19","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41575-019-0158-2","article-title":"New insights into acute pancreatitis.","volume":"16","author":"Lee","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/s1044-579x(02)00128-1","article-title":"NF-\u03baB in cancer: a marked target.","volume":"13","author":"Lin","year":"2003","journal-title":"Semin. Cancer Biol."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105311","article-title":"The pathogenesis of renal injury in obstructive jaundice: a review of underlying mechanisms, inducible agents and therapeutic strategies.","volume":"163","author":"Liu","year":"2021","journal-title":"Pharmacol. Res."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/9857683","article-title":"Anti-inflammatory effects of shenfu injection against acute lung injury through inhibiting hmgb1-nf-\u03bab pathway in a rat model of endotoxin shock.","volume":"2019","author":"Liu","year":"2019","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.intimp.2019.05.005","article-title":"Melatonin alleviates circadian rhythm disruption exacerbating DSS-induced colitis by inhibiting the distribution of HMGB1 in intestinal tissues.","volume":"73","author":"Liu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1111\/hepr.13378","article-title":"Discrepancy between volume and functional recovery in early phase liver regeneration following extended hepatectomy with extrahepatic bile duct resection.","volume":"49","author":"Maeda","year":"2019","journal-title":"Hepatol. Res."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-71756-7","article-title":"Catalytic specificity of the Lactobacillus plantarum cystathionine \u03b3-lyase presumed by the crystallographic analysis.","volume":"10","author":"Matoba","year":"2020","journal-title":"Sci. Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1007\/s00383-020-04762-5","article-title":"The effect of pre- and post-remote ischemic conditioning reduces the injury associated with intestinal ischemia\/reperfusion.","volume":"36","author":"Miyake","year":"2020","journal-title":"Pediatr. Surg. Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1097\/01.mpg.0000228116.52229.7b","article-title":"Serial transverse enteroplasty for management of refractory D-lactic acidosis in short-bowel syndrome.","volume":"43","author":"Modi","year":"2006","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.ajpath.2012.03.039","article-title":"High mobility group box 1 promotes small intestinal damage induced by nonsteroidal anti-inflammatory drugs through toll-like receptor 4.","volume":"181","author":"Nadatani","year":"2012","journal-title":"Am. J. Pathol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.phrs.2010.06.002","article-title":"Hydrogen sulfide and ischemia\u2013reperfusion injury.","volume":"62","author":"Nicholson","year":"2010","journal-title":"Pharmacol. Res."},{"key":"B30","first-page":"164","article-title":"H2S in periodontal immuneinflammatory response and bone loss: a study in rats.","volume":"32","author":"Niederauer","year":"2019","journal-title":"Acta Odontol. Latinoam."},{"key":"B31","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/s0022-4804(03)00308-1","article-title":"Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats.","volume":"115","author":"Ogata","year":"2003","journal-title":"J. Surg. Res."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13368","article-title":"Extended hypoxia-mediated H2S production provides for long-term oxygen sensing.","volume":"228","author":"Olson","year":"2020","journal-title":"Acta Physiol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1017\/S0714980812000104","article-title":"Exercise training reduces inflammatory mediators in the intestinal tract of healthy older adult mice.","volume":"31","author":"Packer","year":"2012","journal-title":"Can. J. Aging"},{"key":"B34","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1152\/japplphysiol.00164.2004","article-title":"The anti-inflammatory effect of exercise.","volume":"98","author":"Petersen","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1139\/h11-064","article-title":"Skeletal muscle apoptotic response to physical activity: potential mechanisms for protection.","volume":"36","author":"Quadrilatero","year":"2011","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"B36","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.freeradbiomed.2007.01.029","article-title":"Systemic adaptation to oxidative challenge induced by regular exercise.","volume":"44","author":"Radak","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"B37","first-page":"71","article-title":"An improvement of the 2^(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis.","volume":"3","author":"Rao","year":"2013","journal-title":"Biostat. Bioinforma. Biomath."},{"key":"B38","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1080\/10641963.2018.1445752","article-title":"Long-term exercise restores hydrogen sulfide in the kidney and contributes to exercise benefits in 5\/6 nephrectomized rats.","volume":"41","author":"Seifi","year":"2019","journal-title":"Clin. Exp. Hypertens."},{"key":"B39","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1089\/ars.2006.8.517","article-title":"Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle.","volume":"8","author":"Song","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"B40","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1189\/jlb.0806540","article-title":"Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1.","volume":"81","author":"Tang","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"746","DOI":"10.2174\/1566524019666190820141331","article-title":"Functional changes of paneth cells in the intestinal epithelium of mice with obstructive jaundice and after internal and external biliary drainage.","volume":"19","author":"Tian","year":"2019","journal-title":"Curr. Mol. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1152\/physrev.00027.2002","article-title":"Bile salt transporters: molecular characterization, function, and regulation.","volume":"83","author":"Trauner","year":"2003","journal-title":"Physiol. Rev."},{"key":"B43","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease.","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"8314","DOI":"10.3748\/wjg.v21.i27.8314","article-title":"TLR4- HMGB1-, MyD88- and TRIF-dependent signaling in mouse intestinal ischemia\/reperfusion injury.","volume":"21","author":"Wang","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1017\/S0007114516004116","article-title":"Dietary live yeast and mannan-oligosaccharide supplementation attenuate intestinal inflammation and barrier dysfunction induced by Escherichia coli in broilers.","volume":"116","author":"Wang","year":"2016","journal-title":"Br. J. Nutr."},{"key":"B46","doi-asserted-by":"publisher","first-page":"4384","DOI":"10.1096\/fj.201900817R","article-title":"HMGB1-associated necroptosis and Kupffer cells M1 polarization underlies remote liver injury induced by intestinal ischemia\/reperfusion in rats.","volume":"34","author":"Wen","year":"2020","journal-title":"FASEB J."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3831713","article-title":"Hydrogen sulfide as a novel regulatory factor in liver health and disease.","volume":"2019","author":"Wu","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B48","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1096\/fj.05-4712fje","article-title":"Pro-apoptotic effect of endogenous H2S on human aorta smooth muscle cells.","volume":"20","author":"Yang","year":"2006","journal-title":"FASEB J."},{"key":"B49","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/s0305-4179(02)00210-3","article-title":"The influence of apoptosis of mucosal epithelial cells on intestinal barrier integrity after scald in rats.","volume":"28","author":"Zhang","year":"2002","journal-title":"Burns"},{"key":"B50","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/jwas.12507","article-title":"Effects of luteinizing hormone-releasing hormone analog injection on intestinal transcriptome in grass carp, Ctenopharyngodon idella.","volume":"49","author":"Zhang","year":"2018","journal-title":"J. World Aquac. Soc."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpb.2019.110335","article-title":"Regulation of triglyceride synthesis by estradiol in the livers of hybrid tilapia (Oreochromis niloticus \u2640\u00d7O. aureus \u2642).","volume":"238","author":"Zhang","year":"2019","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-018-0441-4","article-title":"Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction.","volume":"6","author":"Zhou","year":"2018","journal-title":"Microbiome"},{"key":"B53","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s11033-018-4490-3","article-title":"Nonadditive expression of lipid metabolism pathway-related genes in intestine of hybrids of Nile tilapia females (Oreochromis niloticus) and blue tilapia males (Oreochromis aureus).","volume":"46","author":"Zhou","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"B54","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.gpb.2018.10.002","article-title":"Intestinal microbiota in early life and its implications on childhood health.","volume":"17","author":"Zhuang","year":"2019","journal-title":"Genomics, Proteom. Bioinform."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.732780\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T06:50:19Z","timestamp":1643957419000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2021.732780\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,4]]},"references-count":54,"alternative-id":["10.3389\/fphys.2021.732780"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2021.732780","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,4]]},"article-number":"732780"}}