内源性大麻素系统对丙戊酸诱导的模型鼠孤独症样行为的影响研究  

Effects of endocannabinoid system on autistic behavior in valproic acid-induced rats

作　　者：彭振 刘瑜 曾义源 罗贵宝 程丽霞 李银楚 张瑜珏 邹明扬 PENG Zhen;LIU Yu;ZENG Yi-yuan;LUO Gui-bao;CHENG Li-xia;LI Yin-chu;ZHANG Yu-jue;ZOU Ming-yang(Harbin Medical University,Harbin,Heilongjiang 150081,China;不详)

机构地区：[1]哈尔滨医科大学,黑龙江哈尔滨150081 [2]重庆市疾病预防控制中心 [3]哈尔滨医科大学公共卫生学院儿少卫生与妇幼保健学教研室

出　　处：《中国儿童保健杂志》2022年第11期1191-1197,共7页Chinese Journal of Child Health Care

基　　金：黑龙江省自然科学基金(LH2021H014);黑龙江省大学生创新创业训练计划项目(S202110226076)

摘　　要：目的探讨花生四烯酸甘油酯(2-AG)水平改变对VPA鼠孤独症样行为的影响,为进一步明确孤独症谱系障碍(ASD)病因及发病机制提供依据。方法以VPA诱导ASD模型鼠为研究对象,将实验鼠分为CON组、VPA组、JZL184急性干预组:VPA+40 mg/kg JZL184组(VPA+40AJ)、JZL184慢性干预组:VPA+1 mg/kg JZL184组(VPA+1RJ)、VPA+3 mg/kg JZL184组(VPA+3RJ)和VPA+10 mg/kg JZL184组(VPA+10RJ)。检测各组大鼠的孤独症样行为,采用液相色谱-质谱联用技术检测大鼠海马组织中内源性大麻素(eCBs)水平,采用Western blot检测eCB系统相关受体及代谢酶表达水平。结果VPA组2-AG、AEA水平显著低于CON组(P<0.05),JZL184干预后,VPA+3RJ组和VPA+10RJ组2-AG水平显著升高(P<0.05)。与CON组相比,VPA组埋珠数量、自梳时间及自发活动明显增多,同时社交能力指数和社交偏好指数降低(P<0.05);JZL184干预后,VPA+40AJ组的埋珠个数、自梳时间、自发活动均减少,社交能力指数和社交偏好指数明显增加;VPA+1RJ组的自梳时间减少;VPA+3RJ组的埋珠个数、自梳时间、自发活动均减少,社交偏好指数明显提高;VPA+10RJ组埋珠个数和自梳时间减少,社交偏好指数明显增加(P<0.05)。VPA组海马组织中CB1R、DAGL、MAGLFAAH蛋白表达显著高于CON组(P<0.05)。JZL184干预后,VPA+3RJ组DAGL和MAGL的蛋白表达显著下调,VPA+10RJ组MAGL也显著下调(P<0.05)。结论低eCBs信号与VPA鼠孤独症样行为有关,升高2-AG水平可以改善ASD模型鼠的重复刻板行为、活动过度和社交功能损伤。Objective To investigate the effect of altered 2-arachidonoylglycerol(2-AG)levels on autistic behaviors in VPA-induced rats(ASD model),so as to provide evidence for identifying the etiology of ASD.Methods The rats were divided into CON group,VPA group(ASD),acute JZL184 injection group[VPA+40 mg/kg JZL184 group(VPA+40 AJ)],chronic JZL184 injection group[including VPA+1 mg/kg JZL184 group(VPA+1 RJ),VPA+3 mg/kg JZL184 group(VPA+3 RJ)and VPA+10 mg/kg JZL184 group(VPA+10 RJ)].The ASD-like behavior of rats in each group was assessed.The levels of endocannabinoids(eCBs)in the hippocampus of rats were detected by liquid chromatography-mass spectrometry.Western blot was used to test the expression levels of related receptors and metabolic enzymes in eCB system.Results The levels of 2-AG and AEA in VPA group were significantly lower than those in CON group(P<0.05).After JZL184 intervention,the levels of 2-AG in VPA+3 RJ group and VPA+10 RJ group significantly increased(P<0.05).Compared with the CON group,the number of buried marbles,self-grooming time and spontaneous activities increased significantly in VPA group,and the sociability index and the social preference index decreased(P<0.05).After JZL184 intervention,the number of buried marbles,self-grooming time and spontaneous activities decreased,and the sociability index and the social preference index in VPA+40 AJ group increased significantly,the self-grooming time of the rats in VPA+1 RJ group decreased.After JZL184 intervention,the number of buried marbles,self-grooming time and spontaneous activities decreased,and the social preference index of the rats in VPA+3 RJ group increased significantly.The number of buried marbles and self-grooming time decreased,and the social preference index of the rats in VPA+10 RJ group increased significantly(P<0.05).The protein expressions of CB1 R,DAGL,MAGL and FAAH in VPA group were significantly higher than those in CON group(P<0.05).After JZL184 intervention,the protein expressions of DAGL and MAGL of the rats in VPA+3 RJ group w

关 键 词：孤独症谱系障碍 内源性大麻素 VPA模型鼠 JZL184 

分 类 号：R749.94[医药卫生—神经病学与精神病学]