中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
5期
686-690,691
,共6页
王婷婷%黄菲%吴辉%张蓓蓓%张信诚%吴晓俊%胡之璧
王婷婷%黃菲%吳輝%張蓓蓓%張信誠%吳曉俊%鬍之璧
왕정정%황비%오휘%장배배%장신성%오효준%호지벽
抑郁%嗅球%神经递质%海马%神经营养因子%炎症因子%抗抑郁药
抑鬱%嗅毬%神經遞質%海馬%神經營養因子%炎癥因子%抗抑鬱藥
억욱%후구%신경체질%해마%신경영양인자%염증인자%항억욱약
depression%olfactory bulb%neurotransmit-ter%hippocampus%neurotrophic factor%inflammatory factor%antidepressant
目的:研究双侧嗅球切除对C57BL/6小鼠行为和海马神经递质及抑郁相关基因表达的影响。方法用探针捣毁并用负压吸出小鼠嗅球建立嗅球切除模型,术后18 d开始分别进行强迫游泳、悬尾、旷场、高架迷宫行为学测试,同时应用LC-MS/MS液质联用法检测海马内7种神经递质的变化,实时定量PCR法检测海马抑郁相关基因的表达。结果嗅球切除后小鼠在旷场中的水平运动明显增加(P<0.05),进入高架迷宫开臂的时间明显延长(P<0.01),海马组织中的5-HIAA/5-HT明显降低(P<0.01),Glu/GABA明显增高(P<0.01)。同时海马组织中的BDNF、Trkb、GDNF、CD11 b、TNF-α基因表达明显升高(P<0.05),而TPH2基因表达下调(P<0.05)。结论嗅球切除导致小鼠多种行为学改变,是多种神经传递以及神经营养因子、炎症因子和合成蛋白基因综合作用的结果,提示将该模型作为抗抑郁药物的研发及筛选工具时需要综合考虑多方面因素的影响,从而对实验结果作出科学合理解释。
目的:研究雙側嗅毬切除對C57BL/6小鼠行為和海馬神經遞質及抑鬱相關基因錶達的影響。方法用探針擣燬併用負壓吸齣小鼠嗅毬建立嗅毬切除模型,術後18 d開始分彆進行彊迫遊泳、懸尾、曠場、高架迷宮行為學測試,同時應用LC-MS/MS液質聯用法檢測海馬內7種神經遞質的變化,實時定量PCR法檢測海馬抑鬱相關基因的錶達。結果嗅毬切除後小鼠在曠場中的水平運動明顯增加(P<0.05),進入高架迷宮開臂的時間明顯延長(P<0.01),海馬組織中的5-HIAA/5-HT明顯降低(P<0.01),Glu/GABA明顯增高(P<0.01)。同時海馬組織中的BDNF、Trkb、GDNF、CD11 b、TNF-α基因錶達明顯升高(P<0.05),而TPH2基因錶達下調(P<0.05)。結論嗅毬切除導緻小鼠多種行為學改變,是多種神經傳遞以及神經營養因子、炎癥因子和閤成蛋白基因綜閤作用的結果,提示將該模型作為抗抑鬱藥物的研髮及篩選工具時需要綜閤攷慮多方麵因素的影響,從而對實驗結果作齣科學閤理解釋。
목적:연구쌍측후구절제대C57BL/6소서행위화해마신경체질급억욱상관기인표체적영향。방법용탐침도훼병용부압흡출소서후구건립후구절제모형,술후18 d개시분별진행강박유영、현미、광장、고가미궁행위학측시,동시응용LC-MS/MS액질련용법검측해마내7충신경체질적변화,실시정량PCR법검측해마억욱상관기인적표체。결과후구절제후소서재광장중적수평운동명현증가(P<0.05),진입고가미궁개비적시간명현연장(P<0.01),해마조직중적5-HIAA/5-HT명현강저(P<0.01),Glu/GABA명현증고(P<0.01)。동시해마조직중적BDNF、Trkb、GDNF、CD11 b、TNF-α기인표체명현승고(P<0.05),이TPH2기인표체하조(P<0.05)。결론후구절제도치소서다충행위학개변,시다충신경전체이급신경영양인자、염증인자화합성단백기인종합작용적결과,제시장해모형작위항억욱약물적연발급사선공구시수요종합고필다방면인소적영향,종이대실험결과작출과학합리해석。
Aim To investigate the changes of behav-iors,neurotransmitters and depression related gene ex-pressions in hippocampus of C57BL/6 mice after olfac-tory bulbectomy (OB).Methods Forced swimming test (FST),tail suspension test (TST),open filed test (OFT),and elevated plus maze test (EPMT) were used to evaluate the behavioral changes 18 days after surgery. LC-MS/MS method was employed to measure the hippocampal neurotransmitters.Quantita-tive PCR approach was established to determine the hippocampal gene expressions associated with depres-sion.Results OB mice were hyperactive in OFT (P<0.05 ) accompanied with increased time spent in open arm of EPMT (P<0.01).Meanwhile,the sur-gery led to the reduction of the ratio of 5-HIAA/5-HT (P <0.01 ) but the increase of Glu/GABA (P <0.01 ) in hippocampus.Moreover,OB elevated the gene expressions of BDNF,Trkb,GDNF,CD1 1 b and TNF-αbut down-regulated that of TPH2 in hippocam-pus (P<0.05 ).Conclusion Behavioral alternation of OB mice was a result of comprehensive effect of the changes of neurotransmission and depression related genes,which call us special attention in using OB as an animal model for research and development of anti-depressants.