花生四烯酸甘油酯水平对孤独症模型鼠海马神经炎性反应的影响

doi:10.11852/zgetbjzz2020-1372

中国儿童保健杂志 ›› 2021, Vol. 29 ›› Issue (4): 385-388.DOI: 10.11852/zgetbjzz2020-1372

花生四烯酸甘油酯水平对孤独症模型鼠海马神经炎性反应的影响

刘瑜¹, 刘泽慧², 谢姝¹, 李玲¹, 施梅³, 邹明扬¹, 孙彩虹¹

1.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,黑龙江哈尔滨 150081;
2.大连市第七人民医院精神科;
3.哈尔滨医科大学附属第一医院精神科

收稿日期:2020-07-16 修回日期:2020-11-20 发布日期:2021-04-27 出版日期:2021-04-10
通讯作者: 孙彩虹,E-mail:suncaihong2003@163.com
作者简介:刘瑜(1993-),女,重庆人,硕士在读,主要研究方向为儿童发育障碍及行为问题。
基金资助:
国家自然科学基金项目(81773458,81903348)

Effect of 2-arachidonoylglycerol level on hippocampal neuroinflammatory response in autistic model rats

LIU Yu^*, LIU Ze-hui, XIE Shu, LI Ling, SHI Mei, ZOU Ming-yang, SUN Cai-hong

^*Department of Children's and Adolescent Health,Public Health College,Harbin Medical University,Harbin, Heilongjiang 150081,China

Received:2020-07-16 Revised:2020-11-20 Online:2021-04-10 Published:2021-04-27
Contact: SUN Cai-hong,E-mail:suncaihong2003@163.com

摘要/Abstract

摘要： 目的分析花生四烯酸甘油酯(2-AG)水平升高对孤独症模型鼠海马神经炎性反应的影响,为孤独症谱系障碍(ASD)病因研究提供理论依据。方法以丙戊酸钠(VPA)诱导的孤独症模型鼠为研究对象,分为对照组(CON组)、VPA组、VPA+1 mg/kg JZL184组(VPA+1RJ组)、VPA+3 mg/kg JZL184组(VPA+3RJ组)、VPA+10 mg/kg JZL184组(VPA+10RJ组)。采用液相色谱-质谱联用技术(LC-MS/MS)检测海马组织中2-AG水平;实时荧光定量PCR(RT-PCR)和酶联免疫吸附实验(ELISA)检测海马组织中促炎因子TNF-α、iNOS、IL-1β和抗炎因子Arg-1、IL-4、IL-10和IL-13的mRNA表达水平和组织含量。结果 LC-MS/MS结果显示:VPA组海马组织中2-AG水平显著低于CON组(P＜0.05);VPA+10RJ组2-AG水平显著高于VPA组(P＜0.05)。RT-PCR结果显示:与CON组相比,VPA组中iNOS表达增加(P＜0.05)。与VPA组相比,VPA+1RJ组中IL-1β、Arg-1、IL-10、IL-13表达增加,iNOS表达降低(P<0.05);VPA+3RJ组中TNF-α和iNOS表达降低(P<0.05);VPA+10RJ组中iNOS表达降低,IL-10表达增加(P＜0.05)。ELISA结果显示:与CON组相比,VPA组中iNOS表达上调,Arg-1、IL-10表达降低(P＜0.05)。与VPA组相比,VPA+1RJ组中IL-4表达上调;VPA+3RJ组中iNOS表达降低,IL-10表达上调;VPA+10RJ组中iNOS表达降低,Arg-1、IL-10表达上调(P＜0.05)。结论 2-AG水平的升高可缓解孤独症模型鼠海马组织中存在的异常神经炎性反应。

关键词: 孤独症谱系障碍, 丙戊酸钠, 神经炎性反应, 花生四烯酸甘油酯, 细胞因子

Abstract: Objective To analyze the effect of regulating 2-arachidonoylglycerol(2-AG) level on the expression of cytokines in hippocampus of autistic model rats,in order to provide a theoretical basis for the etiology research of autism spectrum disorders (ASD). Methods Autistic model rats induced by sodium valproate (VPA) were chosen as objects,and were divided into control group (CON group),VPA group,VPA + 1 mg/kg JZL184 group (VPA + 1RJ group),VPA + 3 mg/kg JZL184 group (VPA + 3RJ group),VPA + 10 mg/kg JZL184 group (VPA + 10RJ group). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the level of 2-AG in the hippocampus. Real-time fluorescent quantitative PCR (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA) were used to measure the mRNA expression levels and tissue contents in the hippocampus,including pro-inflammatory cytokines TNF-α,iNOS,IL-1β and anti-inflammatory cytokines Arg-1,IL-4,IL-10 and IL-13. Results LC-MS/MS results showed that the level of 2-AG decreased in hippocampus of VPA rats than that in the CON group (P<0.05),which was significantly higher in VPA+10RJ group than that in VPA group (P<0.05). RT-PCR results showed that compared with the CON group,the expression level of iNOS was increased in the VPA group (P<0.05). Compared with the VPA group,the expression levels of IL-1β,Arg-1,IL-10,IL-13 increased,while the expression level of iNOS decreased in the VPA + 1RJ group. In the VPA+3RJ group,TNF-α and iNOS expression levels decreased than those in VPA group. iNOS expression decreased,and IL-10 expression increased in the VPA + 10RJ group (P<0.05). ELISA results showed that compared with CON group,the expression of iNOS in VPA group was up-regulated,and the expression of Arg-1 and IL-10 was decreased (P<0.05). Compared with the VPA group,the expression of IL-4 in the VPA + 1RJ group was up-regulated,the expression of iNOS was reduced and the expression of IL-10 was up-regulated in the VPA + 3RJ group. In the VPA + 10RJ group,the expression of iNOS was reduced,and the expression of Arg-1 and IL-10 was up-regulated compared with VPA group (P<0.05). Conclusion Elevating 2-AG level could relieve the abnormal neuroinflammation in hippocampus of autistic model rats.

Key words: autism spectrum disorder, valiproic acid, neuroinflammation, 2-arachidonoylglycerol, cytokine

中图分类号:

R285.5

刘瑜, 刘泽慧, 谢姝, 李玲, 施梅, 邹明扬, 孙彩虹. 花生四烯酸甘油酯水平对孤独症模型鼠海马神经炎性反应的影响[J]. 中国儿童保健杂志, 2021, 29(4): 385-388.

LIU Yu, LIU Ze-hui, XIE Shu, LI Ling, SHI Mei, ZOU Ming-yang, SUN Cai-hong. Effect of 2-arachidonoylglycerol level on hippocampal neuroinflammatory response in autistic model rats[J]. Chinese Journal of Child Health Care, 2021, 29(4): 385-388.

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花生四烯酸甘油酯水平对孤独症模型鼠海马神经炎性反应的影响

Effect of 2-arachidonoylglycerol level on hippocampal neuroinflammatory response in autistic model rats

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