口服L-苏糖酸镁预防长春新碱诱导的大鼠记忆和情感障碍  

Oral administration of magnesium-L-threonate prevents vincristine-induced memory and emotional deficits

作　　者：陈佳新 周鑫 熊媖 刘先国[4] 舒海华 CHEN Jia-xin;ZHOU Xin;XIONG Ying;LIU Xian-guo;SHU Hai-hua(School of Medicine South China University of Technology,Guangzhou 510006,China;Department of Anesthesiology,Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,China;Guangdong Cardiovascular Institute,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China;Sun Yat-sen Medical College,Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]华南理工大学医学院,广州510006 [2]南方医科大学附属广东省人民医院(广东省医学科学院)麻醉科,广州510080 [3]广东省心血管病研究所,广东省人民医院,广东省医学科学院,广州510080 [4]中山大学中山医学院,广州510080

出　　处：《中国疼痛医学杂志》2024年第6期413-423,共11页Chinese Journal of Pain Medicine

基　　金：“珠江人才计划”领军人才(KY012023288);中国博士后科学基金第68批面上资助项目(No.2020M682641)。

摘　　要：目的:观察L-苏糖酸镁(magnesium-L-threonate,L-TAMS)对长春新碱(vincristine,VCR)诱导的大鼠记忆和情感障碍的影响并探讨其机制。方法:采用随机数表法将SD大鼠随机分为三组:Control组(饮用正常水并注射等量生理盐水)、VCR组(大鼠腹腔注射长春新碱并饮用正常水)、L-TAMS+VCR组(VCR注射前7天起至实验结束在饮用水中加入L-TAMS),每组5~7只。采用新颖物体识别测试(novel object recognition test,NORT)检测大鼠记忆能力;高架十字迷宫实验(elevated plus-maze test,EPMT)检测大鼠焦虑行为;强迫游泳实验(forced swimming test,FST)检测大鼠抑郁行为。使用在体电生理实验技术记录海马CA3-CA1突触后诱发场电位的幅度;Western blot检测海马内N-甲基-D-天冬氨酸受体(N-Methyl-D-Aspartate-Receptors,NMDARs)亚基NR2B表达的情况;免疫荧光检测海马CA1与前扣带回皮质(anterior cingulate cortex,ACC)内小胶质细胞的表达情况。结果:与Control组比较,VCR组认知系数降低,静止不动时间延长,进入高架十字迷宫开放臂的时间和次数减少,海马CA3-CA1突触后场电位幅度降低,海马内NR2B含量显著降低,海马CA1和ACC内小胶质细胞的表达增多,腹腔注射VCR之前,提前7天直至实验结束口服L-TAMS可预防VCR所引起的上述变化。结论:L-TAMS可通过上调海马突触后膜NMDARs亚基NR2B,逆转VCR引起的CA3-CA1突触后场电位幅度显著降低,改善海马突触传递受损,同时,降低大鼠海马CA1和前扣带回皮质的小胶质细胞表达,减轻神经炎症,进一步预防VCR诱导的记忆和情感功能障碍。Objective:To observe the impact of magnesium-L-threonate(L-TAMS)on vincristine(VCR)-induced memory and emotional deficits in rats and to explore its mechanisms.Methods:SD rats were randomly divided into three groups using the random number table method:the Control group(drinking normal water and receiving an equal amount of saline injection),the VCR group(rats injected intraperitoneally with vincristine and drinking normal water),and the L-TAMS+VCR group(L-TAMS as added to the drinking water from 7 days before VCR injection until the end of the experiment),with 5-7 rats in each group.The novel object recognition test(NORT)assessed the memory of SD rats;the elevated plus-maze test(EPMT)evaluated anxiety behaviors;the forced swimming test(FST)assessed depressive behaviors in SD rats.The amplitude of hippocampal CA3-CA1 postsynaptic evoked field potentials was recorded using in vivo electrophysiological experimental techniques;Western blot determined the expression of N-methyl-D-aspartate receptors(NMDARs)subunit NR2B in the hippocampus.Immunofluorescence evaluated the expression of microglia in the CA1 of hippocampus and anterior cingulate cortex(ACC).Results:Compared to the Control group,the VCR group exhibited a decrease in recognition index,an increase in immobility time,a reduction in the time and frequency of entering the open arms of elevated plus-maze,a decrease in the amplitude of synaptic potentials in the CA3-CA1 region of the hippocampus,a significant reduction of the expression of NR2B in the hippocampus,and an increased expression of glial cells in the CA1 region and the ACC of the hippocampus.Oral administration of L-TAMS starting 7 days prior to intraperitoneal injection of VCR until the end of the experiment prevented the aforementioned changes induced by VCR.Conclusion:L-TAMS can reverse the significant reduction in CA3-CA1 postsynaptic field potentials induced by VCR by upregulating the N-methyl-D-aspartate receptor subunit NR2B in the hippocampal postsynaptic membrane,improving impaired hippocamp

关 键 词：L-苏糖酸镁 长春新碱 记忆情感障碍 海马 前扣带回皮质 突触可塑性 神经炎症 

分 类 号：R965[医药卫生—药理学]