{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:09:03Z","timestamp":1791922143858,"version":"4.3.4"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Xiamen","award":["3502Z20227411"],"award-info":[{"award-number":["3502Z20227411"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Objectives<\/jats:title>\n<jats:p>To investigate the effect of dexamethasone (DXM) on acute lung and kidney injury with sepsis and its possible mechanism.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Control (NC), lipopolysaccharide (LPS) and lipopolysaccharide + dexamethasone (LPS+DXM) treated groups were established by random assignment of 72 Wistar rats. The NC rats were injected with physiological saline, while the LPS group was injected with LPS (5 mg\/kg) and LPS+DXM group was injected with LPS(5 mg\/kg) first and followed by DXM (1 mg\/kg). Serum tumor necrosis factor-\u03b1 (TNF-\u03b1) and serum macrophage inflammatory protein 1\u03b1 (MIP-1\u03b1) were measured by ELISA. Lung wet\/dry weight ratio, serum creatinine(SCR) and blood urea nitrogen(BUN) were determined at various time points. Hematoxylin Eosin staining (HE) for pathological changes in the lung and kidney. Radioimmunoassay was used to detect the levels of angiotensin II (Ang II) in plasma, lung and kidney tissues. Immunohistochemistry and western blot (WB) were used to detect angiotensin II receptor type 1 (AT1R) protein and angiotensin II receptor type 2 (AT2R) protein in lung and kidney tissues. The level of nitric oxide (NO) in serum, lung and kidney were detected using nitrate reductase method.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Compared with control group, serum TNF-\u03b1, MIP-1\u03b1, SCR, BUN, lung W\/D, Ang II level in plasma, lung and kidney, lung and kidney AT2R protein, NO level in serum, lung and kidney were significantly elevated(P&lt;0.05) and pathological damage of lung and kidney tissues were showed in LPS group rats (P&lt;0.05), whereas DXM down-regulated the above indexes and alleviate pathological damage of lung and kidney tissues. However, the expression of the lung and kidney AT1R protein was opposite to the above results.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Sepsis can cause acute lung and kidney injury and changes RAAS components in circulating, lung and renal. DXM can improve acute lung and kidney injury in septic rats, and the mechanism may be related to the down-regulation of inflammatory factors, AngII, AT2R, NO and up-regulation of AT1R expression by DXM.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0308557","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T17:37:57Z","timestamp":1724434677000},"page":"e0308557","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Dexamethasone inhibited angiotensin II and its receptors to reduce sepsis-induced lung and kidney injury in rats"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1109-1502","authenticated-orcid":true,"given":"Zhuqin","family":"Zhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhulan","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8409-6163","authenticated-orcid":true,"given":"Haitao","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"issue":"1","key":"pone.0308557.ref001","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1097\/CCM.0000000000000611","article-title":"Incidence rate of community-acquired sepsis among hospitalized acute medical patients-a population-based survey","volume":"43","author":"DP Henriksen","year":"2015","journal-title":"Crit Care 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independent predictor of mortality in septic acute kidney injury patients treated with continuous renal replacement therapy","volume":"18","author":"IM Han","year":"2017","journal-title":"BMC Nephrol"},{"issue":"50","key":"pone.0308557.ref012","doi-asserted-by":"crossref","first-page":"82602","DOI":"10.18632\/oncotarget.13010","article-title":"Hyperin protects against LPS-induced acute kidney injury by inhibiting TLR4 and NLRP3 signaling pathways","volume":"7","author":"G Chunzhi","year":"2016","journal-title":"Oncotarget"},{"issue":"1","key":"pone.0308557.ref013","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/1465-9921-14-126","article-title":"Inhibition of poly (adenosine diphosphate-ribose) polymeRAASe attenuates lung-kidney crosstalk induced by intratracheal lipopolysaccharide instillation in rats","volume":"14","author":"MK Si","year":"2013","journal-title":"Respir 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Adults with Septic Shock","volume":"378","author":"D Annane","year":"2018","journal-title":"N Engl J Med"},{"issue":"11","key":"pone.0308557.ref021","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.pt.2019.08.007","article-title":"Critical Roles of Endogenous Glucocorticoids for Disease Tolerance in Malaria","volume":"35","author":"L Vandermosten","year":"2019","journal-title":"Trends PaRAASitol"},{"issue":"6","key":"pone.0308557.ref022","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/jlb.67.6.801","article-title":"Dexamethasone promotes phagocytosis and bacterial killing by human monocytes \/ macrophages in vitro","volume":"67","author":"A Van Der Goes","year":"2000","journal-title":"J Leukoc Biol"},{"key":"pone.0308557.ref023","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1164\/rccm.200205-446OC","article-title":"Immunologic and hemodynamic effects of \u201clow-dose\u201d hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study","volume":"167","author":"D Keh","year":"2003","journal-title":"Am J Respir Crit Care Med"},{"key":"pone.0308557.ref024","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jss.2018.02.011","article-title":"Low-dose hydrocortisone prolongs survival in a lethal sepsis model in adrenalectomized rats","volume":"227","author":"T Doulias","year":"2018","journal-title":"J Surg Res"},{"issue":"5","key":"pone.0308557.ref025","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/bcp.12857","article-title":"Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans","volume":"81","author":"J Bartko","year":"2016","journal-title":"Br J Clin Pharmacol"},{"issue":"12","key":"pone.0308557.ref026","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.1111\/jth.13504","article-title":"Dexamethasone inhibits endotoxin-induced coagulopathy in human lungs","volume":"14","author":"J Bartko","year":"2016","journal-title":"J Thromb Haemost"},{"issue":"3","key":"pone.0308557.ref027","first-page":"855","article-title":"Cancer cachexia results in an increase in TNF-alpha receptor gene expression in both skeletal muscle and adipose tissue","volume":"27","author":"M FigueRAAS","year":"2005","journal-title":"Int J Oncol"},{"issue":"1","key":"pone.0308557.ref028","doi-asserted-by":"crossref","first-page":"R24","DOI":"10.1186\/cc8887","article-title":"Renin-angiotensin system activation correlates with microvascular dysfunction in a prospective cohort study of clinical sepsis","volume":"14","author":"KC Doerschug","year":"2010","journal-title":"Crit Care"},{"issue":"5","key":"pone.0308557.ref029","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1097\/SHK.0000000000000807","article-title":"Angiotensin II in Refractory Septic Shock","volume":"47","author":"E Antonucci","year":"2017","journal-title":"Shock"},{"key":"pone.0308557.ref030","doi-asserted-by":"crossref","first-page":"105409","DOI":"10.1016\/j.phrs.2020.105409","article-title":"Therapeutic approaches targeting renin-angiotensin system in sepsis and its complications","volume":"167","author":"L Ning","year":"2021","journal-title":"Pharmacol Res"},{"issue":"6","key":"pone.0308557.ref031","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/j.ajem.2019.03.026","article-title":"Angiotensin II in septic shock","volume":"37","author":"AP Jadhav","year":"2019","journal-title":"Am J Emerg Med"},{"issue":"2","key":"pone.0308557.ref032","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/ajhp\/zxy014","article-title":"Role of angiotensin II in treatment of refractory distributive shock","volume":"76","author":"R Rodriguez","year":"2019","journal-title":"Am J Health Syst Pharm"},{"issue":"5","key":"pone.0308557.ref033","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.3892\/mmr.2017.7546","article-title":"Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system","volume":"16","author":"J Xu","year":"2017","journal-title":"Mol Med Rep"},{"issue":"3","key":"pone.0308557.ref034","doi-asserted-by":"crossref","first-page":"F496","DOI":"10.1152\/ajprenal.00121.2014","article-title":"Alternative pathways for angiotensin II production as an important determinant of kidney damage in endotoxemia","volume":"311","author":"RM Rosa","year":"2016","journal-title":"Am J Physiol Renal Physiol"},{"issue":"9","key":"pone.0308557.ref035","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1042\/CS20130449","article-title":"Recent insights and therapeutic perspectives of angiotensin-(1\u20139) in the cardiovascular system","volume":"127","author":"MP Ocaranza","year":"2014","journal-title":"Clin Sci (Lond)"},{"key":"pone.0308557.ref036","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.biopha.2018.07.170","article-title":"The ACE 2 activator diminazene aceturate (DIZE) improves left ventricular diastolic dysfunction following myocardial infarction in rats","volume":"107","author":"C Castardeli","year":"2018","journal-title":"Biomed Pharmacother"},{"issue":"1","key":"pone.0308557.ref037","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/s13054-018-1995-z","article-title":"Angiotensin in Critical Care","volume":"22","author":"A Hall","year":"2018","journal-title":"Crit Care"},{"issue":"1","key":"pone.0308557.ref038","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1186\/s13054-018-2202-y","article-title":"Angiotensin converting enzyme defects in shock: implications for future therapy","volume":"22","author":"LS Chawla","year":"2018","journal-title":"Crit Care"},{"issue":"1","key":"pone.0308557.ref039","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1177\/1470320309347786","article-title":"The angiotensin II type 2 receptor and the kidney","volume":"11","author":"HM Siragy","year":"2010","journal-title":"J Renin Angiotensin Aldosterone Syst"},{"issue":"6","key":"pone.0308557.ref040","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1258\/ebm.2010.010006","article-title":"Escherichia coli lipopolysaccharide impairs the calcium signaling pathway in mesangial cells: role of angiotensin II receptors","volume":"235","author":"E Maquigussa","year":"2010","journal-title":"Exp Biol Med (Maywood)"},{"issue":"3","key":"pone.0308557.ref041","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1365-2826.2008.01646.x","article-title":"Type 1 angiotensin receptor (AT1-R)-mediated decrease in type 2 angiotensin receptor mRNA level is dependent on Gq and extracellular signal-regulated kinase 1\/\/2 in AT1-R-transfected PC12 cells","volume":"20","author":"M Saito","year":"2008","journal-title":"J Neuroendocrinol"},{"issue":"2","key":"pone.0308557.ref042","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1161\/01.HYP.38.2.177","article-title":"Downregulation of angiotensin II type 1 receptors during sepsis","volume":"38","author":"M Bucher","year":"2001","journal-title":"Hypertension"},{"key":"pone.0308557.ref043","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1161\/01.HYP.31.1.342","article-title":"Downregulation of angiotensin II type 1 receptor gene tranSCRiption by nitric oxide","volume":"31","author":"T Ichiki","year":"1998","journal-title":"Hypertension"},{"key":"pone.0308557.ref044","doi-asserted-by":"crossref","first-page":"856891","DOI":"10.3389\/fmed.2022.856891","article-title":"Corticosteroid Treatment Prevents Lipopolysaccharide-Induced Increase of ACE2 and Reduces Fibrin Degradation Products in Bronchoalveolar Lavage Fluid","volume":"9","author":"R Reindl-Schwaighofer","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"pone.0308557.ref045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2019.01.009","article-title":"Dexmedetomidine protects against lipopolysaccharide-induced early acute kidney injury by inhibiting the iNOS\/NO signaling pathway in rats","volume":"85","author":"Y Chen","year":"2019","journal-title":"Nitric Oxide"},{"key":"pone.0308557.ref046","article-title":"Comparative effects of recombinant human activated protein C","author":"Y Bouazza"},{"issue":"2","key":"pone.0308557.ref047","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3233\/CH-2009-1162","article-title":"Dexamethasone attenuated endotoxin-induced acute lung injury through inhibiting expression of inducible nitric oxide synthase","volume":"41","author":"Z Yu","year":"2009","journal-title":"Clin Hemorheol 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