Article(id=1292765498312258418, tenantId=1146029695717560320, journalId=1291416979304972313, issueId=1291824268032110598, articleNumber=null, orderNo=null, doi=10.3969/j.issn.1005-4847.2026.03.001, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1757952000000, receivedDateStr=2025-09-16, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1786148913218, onlineDateStr=2026-08-08, pubDate=1774800000000, pubDateStr=2026-03-30, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1786148913218, onlineIssueDateStr=2026-08-08, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1786148913218, creator=13701087609, updateTime=1786148913218, updator=13701087609, issue=Issue{id=1291824268032110598, tenantId=1146029695717560320, journalId=1291416979304972313, year='2026', volume='34', issue='3', pageStart='313', pageEnd='468', issueExtLink='null', onlineDate='null', pubDate='1774800000000', pubDateStr='2026-03-30', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=1, specialIssue=null, createTime=1785924506432, creator='ztmeta', updateTime=1786331936953, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1293533155567366441, tenantId=1146029695717560320, journalId=1291416979304972313, issueId=1291824268032110598, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1293533155567366442, tenantId=1146029695717560320, journalId=1291416979304972313, issueId=1291824268032110598, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=313, endPage=325, ext={EN=ArticleExt(id=1292765498496807795, articleId=1292765498312258418, tenantId=1146029695717560320, journalId=1291416979304972313, language=EN, title=Metabolomics-based investigation of phenotypic and traditional Chinese medicine syndrome differences in rat models of chronic stress-related dry eye, columnId=null, journalTitle=Acta Laboratorium Animalis Scientia Sinica, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective To establish and characterize two chronic stress-related dry-eye models using chronic unpredictable mild restraint (CUMR) and chronic unpredictable rhythm disturbance (CURD), respectively, and to compare their phenotypic presentations, metabolomic profiles, and correlations with traditional Chinese medicine syndrome patterns.
Methods Healthy male specific-pathogen-free rats were divided into control, CUMR, and CURD groups. Rats in the CUMR group underwent single-cage housing combined with behavioral restraint daily, while CURD rats received random daily rhythm interventions. After 6 weeks of modeling, dry-eye rats associated with Yu syndrome were assessed for general conditions, behavioral performance, and dry-eye parameters. Histopathological alterations in the conjunctiva, cornea, and lacrimal gland were examined by hematoxylin-eosin staining. Serum concentrations of 5-hydroxytryptamine (5-HT) and cortisol, and cornea levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were quantified by enzyme-linked immunosorbent assay. Serum metabolomic profiling was conducted using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.
Results (1) There were significant differences in appearance and behavior between the CUMR and CURD groups. (2) Compared with the control group, cornea fluorescein staining(CFS) was significantly increased in the CUMR and CURD groups, while tear flow and tear-film breakup time (BUT) were significantly decreased, especially in the CUMR group. (3) There was no obvious inflammatory cell infiltration in the cornea in the CUMR or CURD group. Compared with the control group, there were significantly fewer conjunctival goblet cells in the CUMR and CURD groups, and the area of lacrimal gland vacuolation was significantly increased. (4) Serum 5-HT was significantly decreased and cortisol was significantly increased in the CUMR group compared with the CURD group, but there were no significant differences in cornea tissue TNF-α and IL-1β levels. (5) Serum metabolomic analysis revealed 235 differential metabolites in the CUMR and CURD groups, demonstrating a significant separation trend.
Conclusions Distinct stress-modeling paradigms differentially impact host metabolism, culminating in divergent TCM syndrome manifestations and dry-eye phenotypes. The CUMR model exemplifies a dry-eye phenotype consistent with "Liver Depression and Spleen Deficiency," potentially mediated by perturbations in tryptophan metabolism, while the CURD model aligns with "Stagnation Heat in the Liver Channel," likely arising from disruptions in the tricarboxylic acid cycle.
, authors=Zehai CHEN, Shuwen RUI, Yuanchen DING, Yu PEI, Changchang WANG, Wei SHI
*, Ying YANG
*, authorsList=Zehai CHEN, Shuwen RUI, Yuanchen DING, Yu PEI, Changchang WANG, Wei SHI, Ying YANG, authorCompany=null, correspAuthors=Wei SHI, Ying YANG, authorNote=null, correspAuthorsNote=
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目的 构建慢性不可预测轻度约束（chronic unpredictable mild restraint, CUMR）与慢性不可预测节律干预（chronic unpredictable rhythm disturbance, CURD）两种慢性应激相关干眼模型，比较两种模型的表型和代谢组学特征以及与中医证候的关联。
方法 SPF级健康雄性大鼠分为空白组、CUMR组、CURD组，CUMR组每天施加单笼饲养 + 行为约束，CURD组每天施加随机节律干预。造模6周后，筛选出郁证相关干眼大鼠，评估一般情况、行为学、干眼指标；苏木素-伊红（HE）染色观察结膜、角膜、泪腺病理变化；ELISA法检测血清5-羟色胺（5-HT）、皮质醇（cortisol）和角膜组织肿瘤坏死因子（TNF）-α、白介素（IL）-1β指标水平；超高效液相色谱-四极杆-飞行时间质谱联用系统（UPLC-QTOF-MS）技术进行血清代谢组学分析。
结果 （1）CUMR组和CURD组外观和行为学有显著性差异；（2）CUMR组、CURD组与空白组相比，角膜荧光染色（CFS）显著增加，泪流量（TF）、泪膜破裂时间（BUT）显著减少，且CUMR组改变更为明显；（3）CUMR组、CURD组角膜未见明显炎症细胞浸润。与空白组相比，CUMR组、CURD组结膜杯状细胞数量显著降低、泪腺空泡化面积显著增加，且CUMR组改变更为明显；（4）CUMR组与CURD组ELISA检测比较，CUMR组血清5-HT显著降低，cortisol显著升高、角膜组织TNF-α、IL-1β无统计学意义；（5）血清代谢组学分析提示，CUMR组和CURD组样本中鉴定出235个差异代谢物，呈现显著的分离趋势。
结论 不同的应激造模会影响大鼠代谢，从而造成不同的中医证候和干眼表型。CUMR组表现为“肝郁脾虚型”干眼，其病理进程可能与色氨酸代谢有关；CURD组表现为“肝经郁热型”干眼，其生物学基础可能涉及三羟酸循环。
, authors=陈泽海, 芮书文, 丁园晨, 裴昱, 王畅畅, 施炜
*, 杨颖
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陈泽海，男，在读硕士研究生，研究方向：中西医结合治疗眼病。Email：1473449625@qq.com
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