Article(id=1291404578654777435, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291404554201985968, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2025.06.014, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1730217600000, receivedDateStr=2024-10-30, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785824444687, onlineDateStr=2026-08-04, pubDate=1743091200000, pubDateStr=2025-03-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785824444687, onlineIssueDateStr=2026-08-04, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785824444687, creator=13701087609, updateTime=1785824444687, updator=13701087609, issue=Issue{id=1291404554201985968, tenantId=1146029695717560320, journalId=1246415772164075586, year='2025', volume='41', issue='6', pageStart='751', pageEnd='900', issueExtLink='null', onlineDate='null', pubDate='1743091200000', pubDateStr='2025-03-28', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1785824438858, creator='13701087609', updateTime=1785824438858, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=822, endPage=827, ext={EN=ArticleExt(id=1291404578856104028, articleId=1291404578654777435, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Research on improvement effects of fingolimod on depressive behavior in a rat model of depression disorder, columnId=1246531407326105792, journalTitle=Chinese Journal of Clinical Pharmacology, columnName=Clinical and Basic Bridging Research, runingTitle=null, highlight=null, articleAbstract=
Objective To explore the effect of fingolimod (FTY720) on depressive behavior in depressive disorder rats and its related mechanism.
Methods The SD rats were divided into the following groups: Control group (normal feeding), model group (depression model construction), and low, medium, high groups (administering 0.1, 0.3 and 1.0 mg·kg-1 FTY720 prior to constructing the depression model, respectively), with 10 rats in each group. The hippocampal tissue morphology was assessed using hematoxylin-eosin (HE) staining; depression symptoms were evaluated through the sucrose preference test; cognitive function was assessed using the Morris water maze test; neuronal apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL); levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway-related proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence; dopamine (DA) content in different brain regions was analyzed by high-performance liquid chromatography.
Results After different treatments, the sugar-water preference rates in control, model and low, medium, high groups were (81.95±9.06)%, (59.72±8.32)%, (62.34±7.58)%, (68.08±7.94)% and (79.61±9.25)%, respectively; the escape latencies were (18.73±2.06), (34.25±3.87), (31.64±2.92), (25.97±2.43) and (19.86±1.95) s, respectively; apoptosis rates were (3.93±0.65)%, (28.75±5.94)%, (24.63±3.21)%, (15.27±2.58)% and (6.08±1.74)%, respectively; NLRP3 mRNA relative expression levels were 1.00±0.17, 4.89±0.64, 4.31±0.72, 2.52±0.58 and 1.87±0.25; ASC mRNA relative expression levels were 1.00±0.14, 2.67±0.53, 2.28±0.39, 1.54±0.26 and 1.39±0.21; DA contents in PFC region were (795.42±64.38), (547.93±52.65), (571.08±51.97), (662.45±73.89) and (748.96±81.53) μg·g-1; DA contents in NAc region were (2 186.53±124.97), (1 672.84±109.25), (1 769.65±112.14), (1 904.27±106.63) and (2 065.92±127.58) μg·g-1; DA contents in the VTA region were (1 765.83±108.29), (1 316.73±115.84), (1 378.52±94.36), (1 494.76±103.21) and (1 653.94±108.45) μg·g-1. Compared with the control group, the above indexes in the model group were statistically significant (all P<0.001). Compared with the model group, the above indexes in the middle dose group were statistically significant (all P<0.05). Compared with the model group, the above indexes in the high dose group were statistically significant (all P<0.001).
Conclusion FTY720 can regulate neuronal damage and cognitive function in depressed model rats, and its antidepressant mechanism may be related to inhibiting the activation of NLRP3 inflammasome pathway and increasing the content of DA in the neural circuit of PFC-ARC-VTA.
, authors=Ling GUO, Yong-quan CHEN, Yu-long WANG, Wei-dong YAO, Hao WANG, Wei CHEN, authorsList=Ling GUO, Yong-quan CHEN, Yu-long WANG, Wei-dong YAO, Hao WANG, Wei CHEN, authorCompany=null, correspAuthors=Yong-quan CHEN, 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), CN=ArticleExt(id=1291404579158093917, articleId=1291404578654777435, tenantId=1146029695717560320, journalId=1246415772164075586, language=CN, title=芬戈莫德改善抑郁症模型大鼠抑郁行为的研究, columnId=1246531407485489349, journalTitle=中国临床药理学杂志, columnName=临床与基础桥接研究, runingTitle=null, highlight=null, articleAbstract=
目的 探讨芬戈莫德（FTY720）对抑郁症大鼠模型的抑郁行为的改善效果及相关作用机制。
方法 将SD大鼠分为对照组（正常饲养）、模型组（构建抑郁模型）和低、中、高剂量组（构建抑郁模型前分别给予0.1、0.3和1.0 mg·kg-1FTY720），每组10只。用苏木精-伊红（HE）染色法检测海马组织形态，用糖水偏好实验评估抑郁症状，用Morris水迷宫实验评估认知功能，用原位末端转移酶标记法检测神经元细胞凋亡，用实时荧光定量聚合酶链反应及免疫荧光法检测核苷酸结合寡聚结构域样受体蛋白3（NLRP3）炎症小体通路相关蛋白表达水平、高效液相色谱法检测各脑区多巴胺（DA）含量。
结果 对照组、模型组和低、中、高剂量组的糖水偏好率分别为（81.95±9.06）%、（59.72±8.32）%、（62.34±7.58）%、（68.08±7.94）%和（79.61±9.25）%，逃逸潜伏期分别为（18.73±2.06）、（34.25±3.87）、（31.64±2.92）、（25.97±2.43）和（19.86±1.95）s，凋亡率分别为（3.93±0.65）%、（28.75±5.94）%、（24.63±3.21）%、（15.27±2.58）%和（6.08±1.74）%，NLRP3 mRNA相对表达水平分别为1.00±0.17、4.89±0.64、4.31±0.72、2.52±0.58和1.87±0.25，凋亡相关斑点样蛋白（ASC）mRNA相对表达水平分别为1.00±0.14、2.67±0.53、2.28±0.39、1.54±0.26和1.39±0.21，前额叶皮质区（PFC）DA含量分别为（795.42±64.38）、（547.93±52.65）、（571.08±51.97）、（662.45±73.89）和（748.96±81.53）μg·g-1，伏隔核区（NAc）DA含量分别为（2 186.53±124.97）、（1 672.84±109.25）、（1 769.65±112.14）、（1 904.27±106.63）和（2 065.92±127.58）μg·g-1，腹侧被盖区（VTA）DA含量分别为（1 765.83±108.29）、（1 316.73±115.84）、（1 378.52±94.36）、（1 494.76±103.21）和（1 653.94±108.45）μg·g-1。模型组的上述指标与对照组比较，在统计学上差异均有统计学意义（均P<0.001）；中剂量组的上述指标与模型组比较，在统计学上差异均有统计学意义（均P<0.05）；高剂量组的上述指标与模型组比较，在统计学上差异均有统计学意义（均P<0.001）。
结论 FTY720可调节抑郁模型大鼠的神经元损伤及认知功能，其抗抑郁机制可能与抑制NLRP3炎症小体通路激活、增加PFC-NAc-VTA神经环路中DA的含量有关。
, authors=郭玲, 陈永权, 王玉龙, 姚卫东, 王浩, 陈伟, authorsList=郭玲, 陈永权, 王玉龙, 姚卫东, 王浩, 陈伟, authorCompany=null, correspAuthors=陈永权, authorNote=
郭玲（1989-），女，主治医师，主要从事认知与疼痛方面的工作
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郭玲（1989-），女，主治医师，主要从事认知与疼痛方面的工作
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