菊淀粉型巴戟天寡糖抗创伤后应激障碍行为学评价  

Behavioral evaluation of anti-post-traumatic stress disorder effect of inulin-type oligosaccharides of Morinda officinalis

作　　者：王运慧 尹勇玉 姚俊祺 刘文刚 袁瑾 张黎明 李云峰 WANG Yun-hui;YIN Yong-yu;YAO Jun-qi;LIU Wen-gang;YUAN Jin;ZHANG Li-ming;LI Yun-feng(Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China;State Key Laboratory of Toxicology and Medical Countermeasures,Beijing 100850,China;Medical School of Chinese PLA,Beijing 100853,China;Institute of Military Cognitive and Brain Sciences,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院毒物药物研究所,北京100850 [2]抗毒药物与毒理学国家重点实验室,北京100850 [3]中国人民解放军医学院,北京100853 [4]军事科学院军事医学研究院军事认知与脑科学研究所,北京100850

出　　处：《中国药理学与毒理学杂志》2021年第1期27-35,共9页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81773708);国家自然科学基金(81173036)。

摘　　要：目的用大鼠和小鼠创伤后应激障碍(PTSD)模型评价菊淀粉型巴戟天寡糖(IOMO)对场景恐惧行为和焦虑行为的影响。方法建立大鼠单次延长应激(SPS)模型和小鼠不可逃避足底电击(FS)模型,实验分组均为正常对照组、模型组、模型+舍曲林(Ser)组和模型+不同剂量IOMO组。在大鼠SPS模型中,于造模后每天1次ig给予IOMO 12.5,25和50 mg·kg^(-1)或Ser 15 mg·kg^(-1),连续给药16 d;在小鼠FS模型中,于造模后每天1次ig给予IOMO 25和50 mg·kg^(-1)或Ser 15 mg·kg^(-1),连续给药15 d。以场景恐惧实验评价恐惧行为,以开场实验(OFT)和高架十字迷宫实验(EPMT)评价焦虑样行为。结果在大鼠SPS模型上,与正常对照组相比,模型组大鼠在场景恐惧实验中僵住时间显著增加(P<0.01),在OFT中进入中央区的潜伏期显著延长(P<0.05)、累计次数显著减少(P<0.01),在EPMT中开臂区停留时间百分比和进入次数百分比显著降低(P<0.05);与模型组相比,模型+IOMO 50 mg·kg^(-1)组和模型+Ser 15 mg·kg^(-1)组上述变化均可显著逆转(P<0.05)。在小鼠FS模型上,模型组小鼠在场景恐惧中僵住时间显著高于正常对照组(造模后第10天,P<0.01;第15天,P<0.05),在OFT中进入中央区的潜伏期显著延长,且累计次数和时间显著减少(P<0.05);模型+IOMO 50 mg·kg^(-1)组上述变化显著逆转(P<0.05,P<0.01)。结论IOMO慢性给药可显著降低SPS模型大鼠和FS模型小鼠场景恐惧的表达,缓解焦虑样行为,具有抗PTSD活性。OBJECTIVE To investigate the effect of inulin-type oligosaccharides of Morinda officinalis(IOMO)on contextual fear and anxiety behavior with post-traumatic stress disorder(PTSD)models of rats and mice.METHODS A single prolonged stress(SPS)model of rats and an inescapable electric foot-shock(FS)model of mice were established.The rats and mice were respectively grouped into normal control group,model group,model+sertraline(Ser)group and model+different doses of IOMO group.In the rat SPS model,IOMO 12.5,25 and 50 mg·kg^(-1) or Ser 15 mg·kg^(-1) was ig given to the rats,respectively,for sixteen consecutive days.In the FS model of mice,the mice were ig given IOMO 25 and 50 mg·kg^(-1) or Ser 15 mg·kg for fifteen consecutive days after foot shock.Contextual freezing measurement was used to evaluate fear behaviors.The elevated plus maze test(EPMT)and open field test(OFT)were used to evaluate the changes in anxiety-like behaviors.RESULTS In the rat SPS model,compared with the normal control group,the freezing time of rats in the model group was significantly increased in the contextual fear test(P<0.01),so was the latency to enter the central area(P<0.05),and the total number of times of entry was significantly reduced(P<0.01)in the OFT.The percentage of time spent in the open arms and times of entry into the open arms in the EPMT were both significantly reduced(P<0.05).Ser 15 mg·kg^(-1) and IOMO 50 mg·kg^(-1) significantly reversed these changes.In the mouse FS model,the freezing time was significantly increased in the contextual freezing test(on the10th day after foot shock,P<0.01;on the 15th day after foot shock,P<0.05),so was the latency to enter the central area,but there was a significant decrease in the total number of times of entry and the time spent in the central area(P<0.05)in the OFT.Chronic treatment with IOMO 50 mg·kg^(-1) could reverse the changes mentioned above.CONCLUSION Chronic treatment with IOMO can significantly reduce contextual fear and anxiety behaviors in SPS model rats and FS model mice,

关 键 词：创伤后应激障碍 巴戟天寡糖 单次延长应激模型 足底电击模型 

分 类 号：R964[医药卫生—药理学] R285.5[医药卫生—药学]