Article(id=1308842076356305833, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308841897058198067, articleNumber=null, orderNo=null, doi=10.16438/j.0513-4870.2026-0274, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1773244800000, receivedDateStr=2026-03-12, revisedDate=1777392000000, revisedDateStr=2026-04-29, acceptedDate=null, acceptedDateStr=null, onlineDate=1789981868113, onlineDateStr=2026-09-21, pubDate=1783785600000, pubDateStr=2026-07-12, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1789981868113, onlineIssueDateStr=2026-09-21, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1789981868113, creator=13701087609, updateTime=1789981868113, updator=13701087609, issue=Issue{id=1308841897058198067, tenantId=1146029695717560320, journalId=1189982191388893191, year='2026', volume='61', issue='7', pageStart='2377', pageEnd='2820', issueExtLink='null', onlineDate='null', pubDate='1783785600000', pubDateStr='2026-07-12', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1789981825365, creator='13701087609', updateTime=1789984154811, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1308851667525792021, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308841897058198067, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1308851667525792022, tenantId=1146029695717560320, journalId=1189982191388893191, issueId=1308841897058198067, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=2533, endPage=2543, ext={EN=ArticleExt(id=1308842076574409642, articleId=1308842076356305833, tenantId=1146029695717560320, journalId=1189982191388893191, language=EN, title=Dexmedetomidine improve acute intestinal barrier injury in sepsis by inhibiting NF-κB and ROCK-RhoA pathways via α₂-adrenergic receptors, columnId=1190335348761793317, journalTitle=Acta Pharmaceutica Sinica, columnName=Original Articles, runingTitle=null, highlight=null, articleAbstract=

The structural and functional homeostasis of the intestinal barrier plays a key role in the occurrence and progression of sepsis. As a highly selective α₂-adrenergic receptor agonist, dexmedetomidine is widely used for sedation in sepsis and perioperative periods requiring surgical intervention. Recent studies have shown that it also exerts anti-inflammatory effects; however, whether it can improve acute intestinal barrier injury in sepsis and the underlying mechanism remain unclear. In this study, an acute sepsis mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Evans blue staining, transmission electron microscopy, HE staining, ELISA, and RT-PCR were used to observe the effects of dexmedetomidine (1-6 μg·kg^-1) on intestinal inflammation and barrier function in septic mice. The expression changes of α₂-adrenergic receptors during inflammation, as well as the effects of dexmedetomidine on NF-κB and RhoA/ROCK signaling pathways under LPS stimulation, were further evaluated in mouse intestinal tissues and RAW 264.7 macrophages. The results showed that dexmedetomidine (1-6 μg·kg^-1) administered 6 h after LPS stimulation significantly reduced the levels of inflammatory factors in plasma and intestinal tissues of septic mice, improved intestinal barrier function, and upregulated the expression of tight junction proteins in the small intestine and colon. LPS stimulation downregulated the expression of α₂-adrenergic receptors on macrophages in vivo and in vitro, whereas dexmedetomidine (5-20 nmol·L^-1) reversed this downregulation under inflammatory conditions, inhibited NF-κB pathway activation and inflammatory cytokine secretion in RAW 264.7 cells, and antagonized RhoA/ROCK pathway activation and decreased transepithelial electrical resistance in Caco-2 cells. In conclusion, this study demonstrates that LPS stimulation downregulates α₂-adrenergic receptor expression in macrophages, and dexmedetomidine can upregulate α₂-adrenergic receptors, thereby it may inhibit the NF-κB and RhoA/ROCK pathways, ultimately suppressing inflammation, improving intestinal barrier function, and alleviating acute intestinal barrier injury in sepsis. The animal experiments were approved by the Animal Ethics Committee of Southwest University (Ethics Review No.: IACUC-20260305-12).

, authors=Lei LI¹, Bang-guo ZHANG², Wan CHEN¹, Yu PU³, Yu-lin LIU³, Ji-fen ZHANG³, Shan FENG³, Tao YI^{4, *}, authorsList=Lei LI, Bang-guo ZHANG, Wan CHEN, Yu PU, Yu-lin LIU, Ji-fen ZHANG, Shan FENG, Tao YI, authorCompany=null, correspAuthors=Tao YI, authorNote=null, correspAuthorsNote=null, copyrightStatement=Copyright ©2026 Acta Pharmaceutica Sinica. All rights reserved., copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1308842080076653504, articleId=1308842076356305833, tenantId=1146029695717560320, journalId=1189982191388893191, language=CN, title=右美托咪定经α₂肾上腺素受体抑制NF-κB和ROCK-RhoA通路改善脓毒症急性肠道屏障损伤的机制研究, columnId=1190335348896011050, journalTitle=药学学报, columnName=研究论文, runingTitle=null, highlight=null, articleAbstract=

肠道屏障的结构与功能稳态在脓毒症的发生发展中起着关键作用。右美托咪定作为高选择性的α₂肾上腺素受体激动剂, 广泛用于脓毒症和围手术期中需要手术干预的镇静治疗。最新研究显示其还具抗炎作用, 但是否能因此改善脓毒症急性期肠道屏障损伤及其机制尚未知。本研究通过腹腔注射脂多糖(lipopolysaccharide, LPS) 构建急性脓毒症小鼠模型, 经Evans染色、透射电镜、HE染色、ELISA和RT-PCR等方法观察了右美托咪定(1~6 μg·kg^-1) 对脓毒症小鼠肠道炎症和屏障改善情况。进一步在小鼠肠道组织和巨噬细胞RAW264.7中评价了α₂肾上腺素受体在炎症过程中的表达变化, 以及右美托咪定对LPS刺激下NF-κB和RhoA/ROCK信号通路的影响。研究结果显示, 右美托咪定(1~6 μg·kg^-1) 在LPS刺激6 h后, 可显著抑制脓毒症小鼠血浆和肠道组织中的炎症因子水平, 改善肠道屏障功能, 上调小肠和结肠组织的紧密连接蛋白表达。LPS刺激可降低体内外巨噬细胞上α₂肾上腺素受体表达, 而右美托咪定(5~20 nmol·L^-1) 可逆转炎症环境下α₂肾上腺素受体表达下调, 抑制RAW264.7中NF-κB通路激活和细胞炎症因子分泌增加, 拮抗Caco-2细胞中RhoA/ROCK信号通路激活及细胞跨膜电阻降低。综上, 本研究证实LPS刺激下巨噬细胞中α₂肾上腺素受体表达下调, 而右美托咪定可回调α₂肾上腺素受体, 并可能经该受体抑制NF-κB和RhoA/ROCK通路, 最终抑制炎症, 改善脓毒症急性期的屏障功能损伤。动物实验经西南大学试验动物伦理委员会批准(伦理审查号: IACUC-20260305-12)。

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A: The mRNA level of inflammatory cytokine in RAW264.7 cells after LPS stimulation; B: The level of inflammatory cytokine in plasma after administrated mice to LPS (ip). n = 3, x ± s. ^##P < 0.01 vs control; ^**P < 0.01 vs LPS. HC: Hydrocortisone; Dex: Dexmedetomidine; LPS: Lipopolysaccharide, figureFileSmall=fRJ5m/9xYPlCbNvqlXRzuA==, figureFileBig=XLhgF9xM1x19ZBDQ35D3UQ==, tableContent=null), ArticleFig(id=1308842085114011648, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=EN, label=null, caption=null, figureFileSmall=CX0hBTGJj029OJuDuJ+QwA==, figureFileBig=pHwP6rXH2eCb3IfxW/e9Gg==, tableContent=null), ArticleFig(id=1308842085172731905, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=CN, label=Fig.2, caption=Effects of Dex treatment on LPS-induced intestinal inflammation. A: HE staining of jejunum; B: HE staining of colon; C: The mRNA level of inflammatory cytokine in jejunum; D: The mRNA level of inflammatory cytokine in colon. n = 3, x ± s. ^##P < 0.01 vs control; ^*P < 0.05, ^**P < 0.01 vs LPS. 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Red arrows point to the epithelial cells; yellow arrows to the tight junctions; blue arrows to the mitochondria; green arrows to the lysosomes, figureFileSmall=V5WV6vmPKlnSgXRskP7yfA==, figureFileBig=Y+Pf5mGjv0vHELhreN5upw==, tableContent=null), ArticleFig(id=1308842085512470534, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=EN, label=null, caption=null, figureFileSmall=zqFhgYQHiQm9wjSiXTm8+w==, figureFileBig=KAldns9diNsMcJXNoX0KXg==, tableContent=null), ArticleFig(id=1308842085592162311, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=CN, label=Fig.5, caption=Transmission electron microscopy analysis of colon. Red arrows point to the epithelial cells; yellow arrows to the tight junctions; blue arrows to the mitochondria; green arrows to the lysosomes, figureFileSmall=zqFhgYQHiQm9wjSiXTm8+w==, figureFileBig=KAldns9diNsMcJXNoX0KXg==, tableContent=null), ArticleFig(id=1308842085671854088, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=EN, label=null, caption=null, figureFileSmall=jSY/i1X0s3igl4jKIIA0sQ==, figureFileBig=ABjOQGc1V3fepjrK/7/PsA==, tableContent=null), ArticleFig(id=1308842085738962953, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=CN, label=Fig.6, caption=Effects of Dex treatment on LPS-induced intestinal barrier destruction. A: Jejunum was stained with antibodies against ZO-1 (green) and DAPI (blue); B: Tight junction protein mRNA expression in jejunum. n = 3, x ± s. ^#P < 0.05, ^##P < 0.01 vs control; ^**P < 0.01 vs LPS, figureFileSmall=jSY/i1X0s3igl4jKIIA0sQ==, figureFileBig=ABjOQGc1V3fepjrK/7/PsA==, tableContent=null), ArticleFig(id=1308842085818654730, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=EN, label=null, caption=null, figureFileSmall=HST9j+13iaq4t8gEPA+nLw==, figureFileBig=TmbNt87aPisXtfZkIYoyCw==, tableContent=null), ArticleFig(id=1308842085902540811, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=CN, label=Fig.7, caption=Effects of Dex treatment on LPS-induced intestinal barrier destruction. A: Colon was stained with antibodies against ZO-1 (green) and DAPI (blue); B: Tight junction protein mRNA expression in colon. n = 3, x ± s. ^#P < 0.05, ^##P < 0.01 vs control; ^*P < 0.05, ^**P < 0.01 vs LPS, figureFileSmall=HST9j+13iaq4t8gEPA+nLw==, figureFileBig=TmbNt87aPisXtfZkIYoyCw==, tableContent=null), ArticleFig(id=1308842085986426892, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=EN, label=null, caption=null, figureFileSmall=iMqgYKcLS5YRMMvtPZoRXQ==, figureFileBig=eiBb/tHq64fmj0LMYkdNrw==, tableContent=null), ArticleFig(id=1308842086066118669, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=CN, label=Fig.8, caption=Effects of Dex treatment on LPS-induced α₂-AR expression downregulation. A: Jejunum was stained with antibodies against α₂-AR (green) and DAPI (blue); B: α₂-AR mRNA expression in RAW264.7 cells after LPS stimulation. n = 3, x ± s. ^**P < 0.01 vs LPS, figureFileSmall=iMqgYKcLS5YRMMvtPZoRXQ==, figureFileBig=eiBb/tHq64fmj0LMYkdNrw==, tableContent=null), ArticleFig(id=1308842086137421838, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=EN, label=null, caption=null, figureFileSmall=0bafoqbODtAlQ+MuT04zQQ==, figureFileBig=YUuMyzwPm02RO3S59p3k0Q==, tableContent=null), ArticleFig(id=1308842086204530703, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=CN, label=Fig.9, caption=Effects of Dex treatment on LPS-induced NF-κB pathway activation. A: RAW264.7 cell was stained with antibodies against CD86 (red) and DAPI (blue); B: IL-1β, TNF-α and IL-6 mRNA expression in RAW264.7 cells after LPS stimulation; C: RAW264.7 cell was stained with antibodies against NF-κB-p65 (green). n = 3, x ± s. ^##P < 0.01 vs control; ^**P < 0.01 vs LPS, figureFileSmall=0bafoqbODtAlQ+MuT04zQQ==, figureFileBig=YUuMyzwPm02RO3S59p3k0Q==, tableContent=null), ArticleFig(id=1308842086288416784, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=EN, label=null, caption=null, figureFileSmall=2yUfAtlXMN+Dh8VYWxArzA==, figureFileBig=jpkUB0rehikDTw2PGWJUOg==, tableContent=null), ArticleFig(id=1308842086368108561, tenantId=1146029695717560320, journalId=1189982191388893191, articleId=1308842076356305833, language=CN, label=Fig.10, caption=Effects of Dex treatment on LPS-induced RhoA-ROCK pathway activation in Caco-2 cell. 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