中国药理学通报
中國藥理學通報
중국약이학통보
CHINESE PHARMACOLOGICAL BULLETIN
2015年
4期
560-564
,共5页
曹秦%黄菲%王婷婷%兰云意%吴辉%张蓓蓓%胡之璧%吴晓俊
曹秦%黃菲%王婷婷%蘭雲意%吳輝%張蓓蓓%鬍之璧%吳曉俊
조진%황비%왕정정%란운의%오휘%장배배%호지벽%오효준
FXR%胆汁酸%神经行为%神经递质%神经传递%情绪
FXR%膽汁痠%神經行為%神經遞質%神經傳遞%情緒
FXR%담즙산%신경행위%신경체질%신경전체%정서
FXR%bile acid%neurobehavior%neuro-transmitter%neurotransmission%emotion
目的:探讨法尼醇 X 受体(farnesoid X receptor,FXR)作为一种核激素受体对情感、社交或记忆等神经行为的调节作用。方法通过一系列行为学测试,包括高架十字迷宫,强迫游泳、社交活动和避暗,以及 LC-MS /MS 法检测大脑不同区域的神经递质,评估 FXR 基因敲除(knockout,KO)对♀小鼠中枢神经系统功能的影响。结果FXR KO 导致小鼠在强迫游泳中不动时间延长(P <0.01),进入高架十字迷宫开放臂次数增加(P <0.01),逗留时间延长,同时社交活动增强(P <0.01),但对避暗行为中的潜伏期和错误次数无明显影响。FXR KO 亦导致小鼠海马γ-氨基丁酸(GABA,P <0.05)、谷氨酸(Glu,P <0.05)、去甲肾上腺素(NE,P <0.01)以及 GABA /Glu(P <0.05)明显降低,但对前额叶相关神经递质无明显影响。结论 FXR 可能参与调控中枢神经系统中神经递质稳态平衡,进而影响动物的情感和社交行为。
目的:探討法尼醇 X 受體(farnesoid X receptor,FXR)作為一種覈激素受體對情感、社交或記憶等神經行為的調節作用。方法通過一繫列行為學測試,包括高架十字迷宮,彊迫遊泳、社交活動和避暗,以及 LC-MS /MS 法檢測大腦不同區域的神經遞質,評估 FXR 基因敲除(knockout,KO)對♀小鼠中樞神經繫統功能的影響。結果FXR KO 導緻小鼠在彊迫遊泳中不動時間延長(P <0.01),進入高架十字迷宮開放臂次數增加(P <0.01),逗留時間延長,同時社交活動增彊(P <0.01),但對避暗行為中的潛伏期和錯誤次數無明顯影響。FXR KO 亦導緻小鼠海馬γ-氨基丁痠(GABA,P <0.05)、穀氨痠(Glu,P <0.05)、去甲腎上腺素(NE,P <0.01)以及 GABA /Glu(P <0.05)明顯降低,但對前額葉相關神經遞質無明顯影響。結論 FXR 可能參與調控中樞神經繫統中神經遞質穩態平衡,進而影響動物的情感和社交行為。
목적:탐토법니순 X 수체(farnesoid X receptor,FXR)작위일충핵격소수체대정감、사교혹기억등신경행위적조절작용。방법통과일계렬행위학측시,포괄고가십자미궁,강박유영、사교활동화피암,이급 LC-MS /MS 법검측대뇌불동구역적신경체질,평고 FXR 기인고제(knockout,KO)대♀소서중추신경계통공능적영향。결과FXR KO 도치소서재강박유영중불동시간연장(P <0.01),진입고가십자미궁개방비차수증가(P <0.01),두류시간연장,동시사교활동증강(P <0.01),단대피암행위중적잠복기화착오차수무명현영향。FXR KO 역도치소서해마γ-안기정산(GABA,P <0.05)、곡안산(Glu,P <0.05)、거갑신상선소(NE,P <0.01)이급 GABA /Glu(P <0.05)명현강저,단대전액협상관신경체질무명현영향。결론 FXR 가능삼여조공중추신경계통중신경체질은태평형,진이영향동물적정감화사교행위。
Aim To investigate how Farnesoid X re-ceptor (FXR),a nuclear hormone receptor,acts on neurological behaviors such as emotion,social behav-ior,memory and so on.Methods FXR’s function in central nervous system was evaluated by conducting a battery of behavioral tests including elevated plus maze test (EPMT),forced-swimming test (FST),social in-teraction test (SIT ), and passive avoidance test (PAT),and the contents of neurotransmitters were de-termined by the LC-MS /MS method in FXR knockout (KO)female mice and their wild-type controls.Re-sults FXR KO mice showed significantly increased immobility time in FST (P <0.01 ),and it showed in-creased tendency to enter the open arms in EMPT (P<0.01 ).The number of probing the open arms by FXR KO mice was more than that of the controls.Mo-reover,in SIT,FXR KO mice had remarkably in-creased sniffing interactions with the stranger mouse in the same cage (P <0.01 ).But in PAT,the latency for FXR KO mice to enter the dark chamber on the test day and the number of FXR KO mice to enter the dark chamber didn’t differ from those wild-type mice.In hippocampus,the contents of GABA,Glu,and NE were decreased prominently in FXR KO mice (P <0.05,P <0.05 and P <0.01 ,respectively)as well as the ratio of GABA to Glu (P <0.05).But in pre-frontal cortex,none of the neurotransmitters examined showed any difference between FXR KO mice and their controls.Conclusion FXR may be involved in main-tenance of the homeostasis of neural transmission in the central nervous system,thereby influences the emotion-al and social behavior in animals.