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

doi:10.11852/zgetbjzz2021-1865

中国儿童保健杂志 ›› 2022, Vol. 30 ›› Issue (11): 1191-1197.DOI: 10.11852/zgetbjzz2021-1865

所属专题：孤独症谱系障碍

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

彭振¹, 刘瑜², 曾义源¹, 罗贵宝¹, 程丽霞¹, 李银楚¹, 张瑜珏³, 邹明扬³

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

收稿日期:2021-12-14 修回日期:2022-04-14 发布日期:2022-11-09 出版日期:2022-11-10
通讯作者: 邹明扬,E-mail:mingyangshine@sina.com
作者简介:彭振(1999-),女,黑龙江人,本科在读,主要研究方向为儿童发育障碍及行为问题。
基金资助:
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)

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

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

Received:2021-12-14 Revised:2022-04-14 Online:2022-11-10 Published:2022-11-09
Contact: ZOU Ming-yang, E-mail:mingyangshine@sina.com

摘要/Abstract

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。

关键词: 孤独症谱系障碍, 内源性大麻素, VPA模型鼠, JZL184

Abstract: 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+40AJ)], chronic JZL184 injection group [including VPA+1 mg/kg JZL184 group(VPA+1RJ), VPA+3 mg/kg JZL184 group(VPA+3RJ) and VPA+10 mg/kg JZL184 group(VPA+10RJ) ]. 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+3RJ group and VPA+10RJ 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+40AJ group increased significantly, the self-grooming time of the rats in VPA+1RJ 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+3RJ group increased significantly. The number of buried marbles and self-grooming time decreased, and the social preference index of the rats in VPA+10RJ group increased significantly(P<0.05).The protein expressions of CB1R, 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+3RJ group were significantly down-regulated, and MAGL in VPA+10RJ group were also significantly down-regulated(P<0.05). Conclusions Low eCBs signal is associated with autistic behaviors in VPA-induced rats, and boosting 2-AG levels can improve repetitive and stereotypical behaviors, hyperactivity and social functions in ASD rats.

Key words: autism spectrum disorder, endocannabinoids, VPA-induced rats, JZL184

中图分类号:

R749.94

彭振, 刘瑜, 曾义源, 罗贵宝, 程丽霞, 李银楚, 张瑜珏, 邹明扬. 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[J]. 中国儿童保健杂志, 2022, 30(11): 1191-1197.

PENG Zhen, LIU Yu, ZENG Yi-yuan, LUO Gui-bao, CHENG Li-xia, LI Yin-chu, ZHANG Yu-jue, ZOU Ming-yang. Effects of endocannabinoid system on autistic behavior in valproic acid-induced rats[J]. Chinese Journal of Child Health Care, 2022, 30(11): 1191-1197.

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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

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