磁石煅制调节肠道菌群-神经递质/炎症因子抗抑郁作用及机制研究  

Research on antidepressant effect and mechanism of magnet processed regulating intestinal microbiota-neurotransmitter/inflammatory factors

作　　者：宋学姣 林文涵 庄朋伟 尹清晟 柴士伟[2,3] SONG Xuejiao;LIN Wenhan;ZHUANG Pengwei;YIN Qingsheng;CHAI Shiwei(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China;National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion,Tianjin 300381,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津中医药大学第一附属医院,天津300381 [3]国家中医针灸临床医学研究中心,天津300381

出　　处：《天津中医药》2024年第11期1452-1458,共7页Tianjin Journal of Traditional Chinese Medicine

基　　金：天津市卫生健康委员会中医、中西医结合科研专项课题(2021013);2024年全国中药特色技术传承人才项目培训(1128022-2024)。

摘　　要：[目的]明确磁石煅制对其抗抑郁作用的影响,并基于肠道菌群-神经递质/炎症因子探讨其机制。[方法]采用慢性不可预知温和性应激(CUMS)诱导大鼠焦虑和抑郁样行为,并将实验分为空白组、模型组、生磁石组、煅磁石组和阳性对照组,生磁石组、煅磁石组、阳性对照组大鼠每日分别灌胃给予3.15、3.15和0.63 mg/kg生磁石、煅磁石和艾司唑仑,空白组和模型组大鼠给予等体积蒸馏水,连续治疗3周。采用糖水偏好实验、旷场实验和高架十字迷宫实验评估大鼠焦虑和抑郁行为;采用高效液相色谱-电化学系统(HPLC-ECD)检测皮质单胺类神经递质多巴胺(DA)、5-羟色胺(5-HT)、去甲肾上腺素(NE)及5-羟基吲哚乙酸(5-HIAA)含量;采用实时荧光定量聚合酶链反应(qPCR)检测海马组织炎症因子白介素-18(IL-18)、白介素-6(IL-6)和白介素-1β(IL-1β)mRNA水平;采用16S rRNA测序肠道微生物结构和组成变化。[结果]与正常组相比,模型组大鼠糖水偏好率、旷场直立次数以及进入高架十字迷宫开臂的次数和时间均显著降低(P<0.05),皮质神经递质(5-HT、NE和5-HIAA)含量显著降低(P<0.05),海马促炎因子(IL-18、IL-6和IL-1β)mRNA水平显著升高(P<0.05),肠道菌群结构和组成紊乱;与模型组相比,生、煅磁石组大鼠糖水偏好率及进入高架十字迷宫开臂的次数和时间均显著增加(P<0.05),煅磁石组大鼠在旷场中直立次数增多(P<0.05);煅磁石组大鼠脑皮层神经递质含量增加,肠菌中乳杆菌(Lactobacillus)、罗伊氏乳杆菌(Limosilactobacillus)、拟杆菌(Bacteroides)丰度显著升高(P<0.05),生磁石组大鼠海马组织促炎因子(IL-6和IL-1β)mRNA水平显著降低(P<0.05),肠菌中Christensenellaceae_R-7_group、NK4A214_group、罗氏菌(Roseburia)丰度显著升高。[结论]生、煅磁石均有改善CUMS大鼠焦虑和抑郁样行为的作用,煅磁石通过调控肠道乳杆菌、拟杆菌等增加脑神经递质含量相关,而�[Objective]To clarify the effect of calcined magnet on its antidepressant effect,and to explore its mechanism based on intestinal flora-neurotransmitter/inflammatory factors.[Methods]Chronic unpredicted mild stress(CUMS)was used to induce anxiety and depression-like behavior in rats.The rats were divided into blank group,model group,raw magnet group,calcined magnet group and positive control group.The rats in the raw magnet group,calcined magnet group and positive control group were given 3.15 g/kg,3.15 g/kg and 0.63 mg/kg raw magnet,calcined magnet and estazolam by intragastric administration every day.The rats in the blank group and the model group were given equal volume of distilled water for 3 weeks.Sucrose preference test,open field test and elevated plus maze test were used to evaluate the anxiety and depression behavior of rats.The contents of monoamine neurotransmitters dopamine(DA),5-hydroxytryptamine(5-HT),norepinephrine(NE)and 5-hydroxyindole acetic acid(5-HIAA)in cortex were detected by HPLC-ECD.The levels of inflammatory factors interleukin-18(interleukin-18,IL-18)、interleukin-6(interleukin-6,IL-6)and interleukin-1β(interleukin-1β,IL-1β)mRNA in hippocampus were detected by qPCR.The changes of intestinal microbial structure and composition were analyzed by 16S rRNA sequencing.[Results]Compared with the normal group,the sucrose preference rate,the number of rearing in the open field,the number and time of entering the open arm of the elevated plus maze in the model group were significantly decreased(P<0.05),the contents of cortical neurotransmitters(5-HT,NE and 5-HIAA)were significantly decreased(P<0.05),the mRNA levels of hippocampal pro-inflammatory factors(IL-18,IL-6 and IL-1β)were significantly increased(P<0.05),and the structure and composition of intestinal flora were disordered.Compared with the model group,the sucrose preference rate and the number and time of entering the open arm of the elevated plus maze were significantly increased in the raw and calcined magnet groups(P<0.05).The nu

关 键 词：磁石 炮制 抑郁 肠道菌群 神经递质 炎症 

分 类 号：R285.5[医药卫生—中药学]