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tenantId=1146029695717560320, journalId=1315121837170065538, language=CN, title=基于肠道菌群探讨加味丹栀逍遥散抗抑郁的作用机制, columnId=null, journalTitle=中医学报, columnName=实验研究, runingTitle=null, highlight=null, articleAbstract=目的:基于肠道菌群调节探讨加味丹栀逍遥散对皮质酮（corticosterone,CORT）诱导的抑郁模型小鼠的抗抑郁作用机制。方法:将50只C57BL/6J雄性小鼠随机分为5组:正常组、模型组、氟西汀组、加味丹栀逍遥散低剂量组、加味丹栀逍遥散高剂量组，每组10只。采用皮下注射CORT(20 mg·kg⁻¹)制备抑郁模型，造模第5周开始，各给药组分别灌胃给予相应药物，正常组和模型组给予等体积蒸馏水，持续干预至第8周。通过蔗糖偏好实验、旷场实验和高架十字迷宫实验评价小鼠抑郁样行为;采用酶联免疫吸附测定法（enzyme-linked immunosorbent assay,ELISA）检测血清CORT、促肾上腺皮质激素释放激素（corticotropin releasing hormone,CRH）、促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）及炎症因子水平;通过16S r DNA测序分析肠道菌群组成与结构;采用苏木素-伊红（hematoxylin-eosin,HE）染色观察结肠组织病理变化，尼氏染色观察海马组织病理变化;通过免疫荧光法和蛋白免疫印迹（Western blot）法检测结肠紧密连接蛋白Occludin的表达。结果:与正常组对比，模型组小鼠糖水偏好率、运动总距离、中心区域停留时间、开放臂停留时间及进入开放臂次数均显著降低（均P<0.05），血清CORT、CRH、ACTH、脂多糖（lipopolysaccharide,LPS）以及促炎因子肿瘤坏死因子-α（tumor necrosis factor-alpha,TNF-α）、干扰素-γ（interferon-gamma,IFN-γ）、白细胞介素-1β（interleukin-1 beta,IL-1β）、白细胞介素-6（interleukin-6,IL-6）、白细胞介素-17（interleukin-17,IL-17）水平显著升高（P<0.05），抗炎因子白细胞介素-4（interleukin-4,IL-4）、白细胞介素-10（interleukin-10,IL-10）水平显著降低（P<0.05），肠道菌群中脱铁杆菌门（Deferribacterota）等有害菌相对丰度显著升高（P<0.05），海马与结肠组织出现显著病理损伤，结肠Occludin蛋白表达显著下调（P<0.05）。与模型组对比，加味丹栀逍遥散高剂量组上述行为学指标均显著改善（均P<0.05），血清神经激素与促炎因子水平显著降低（P<0.05），抗炎因子水平显著升高（P<0.05），肠道菌群结构趋于正常，有害菌丰度降低，海马与结肠组织病理损伤减轻，结肠Occludin蛋白表达显著上调（P<0.05）。相关性分析显示，血清神经激素、炎症因子与特定肠道菌群相对丰度存在显著相关性。结论:加味丹栀逍遥散可能通过调节肠道菌群结构，恢复肠屏障功能，减轻全身及神经炎症，从而改善CORT诱导的抑郁样行为。, authors=null, authorsList=null, authorCompany=null, correspAuthors=null, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, 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)}, 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