Toll样受体4拮抗剂厄立特兰对抑郁症大鼠前额叶和海马神经元发生和γ-氨基丁酸谷氨酸平衡的影响  

Effect of toll-like receptor 4 antagonist erlituran on the occurrence of neurons in the frontal lobe and hippocampus and the balance of glutamate glutathionate in rats with depression

作　　者：丁迎 戢汉斌 陈钰 苏邹 DING Ying;JI Hanbin;CHEN Yu;SU Zou(Department of Rehabilitation,Wuhan Wudong Hospital(the Second Psychiatric Hospital of Wuhan),Wuhan 430084,China)

机构地区：[1]湖北省武汉市武东医院(武汉市第二精神病医院)康复科,武汉430084

出　　处：《实用医学杂志》2018年第23期3893-3897,共5页The Journal of Practical Medicine

基　　金：武汉市卫生计生科研基金资助(编号:WG16D13)

摘　　要：目的探讨Toll样受体4拮抗剂厄立特兰(TAK-242)对抑郁症大鼠模型前额叶(mPFC)和海马神经元发生和γ-氨基丁酸谷氨酸平衡的影响。方法采用随机法将60只雄性SD大鼠分为2批,每批SD大鼠随机分为3组:正常对照组(Control组)、模型组[用长期轻度不可预见性应激(CUMS)加孤养复制大鼠抑郁症模型,Model组]和治疗组[Model+TAK-242(3 mg/kg)]。第1批30只大鼠用于自发活动和强迫游泳测试;第二批30只大鼠用于ELISA法检测大鼠内侧前额叶皮质和海马中5-羟色胺(5-HT)、γ-氨基丁酸(GABA)及谷氨酸(Glu)含量的变化,以及采用Western印迹法检测大鼠内侧前额叶皮质(mPFC)和海马组织中TLR4蛋白的表达情况。结果与正常对照组相比,抑郁症模型组大鼠自发活动减少(P <0.01),强迫游泳不动时间延长(P <0.01);与正常对照组相比,抑郁症模型组大鼠mPFC和海马Glu的含量升高(P <0.05),5-HT和GABA的含量降低(P <0.05);与正常对照组相比,抑郁症模型组大鼠mPFC和海马的TLR4蛋白表达上调(P <0.01)。Model+TAK-242组各项指标与正常对照组相比差异无统计学意义(P>0.05)。结论应用CUMS方法成功建立了抑郁症大鼠模型,抑郁症模型大鼠m PFC和海马存在Glu和GABA递质系统功能紊乱,TLR4蛋白表达上调,加重了继发性的脑损伤;给予TAK-242进行干预后,可改善上述神经递质异常,降低TLR4的激活,改善抑郁症大鼠的学习和记忆功能,具有一定神经保护作用。Objective To discuss the effect of toll-like receptor 4 antagonist erlituran on the occurrence of neurons in the frontal lobe and hippocampus and the balance of glutamate glutathionate in rats with depression.Methods Sixty male SD rats were randomly divided into two batches.SD rats in each batch were randomly divid-ed into 3 groups:normal control group,model group[with chronic mild stress(CUMS)unpredictability isolated copy depression model rats]and the treatment group[Model+TAK-242(3 mg/kg)].The first batch of 30 rats were used for voluntary activity and forced swimming tests.For the second batch of 30 rats,the ELISA method was used to detect the changes in the contents of 5-HT,GABA and Glu in the medial prefrontal cortex and hippocampus.The expression of TLR4 protein in the medial prefrontal cortex(mPFC)and hippocampus of rats was detected by Western blotting.Results Compared with the control group,the spontaneous activity of rats in the depression model group was significantly reduced(P<0.01)and the forced swimming time was significantly prolonged(P<0.01).Compared with the control group,the contents of mPFC and hippocampal Glu in the depression model group increased significantly(P<0.05),and the contents of 5-HT and GABA were significantly decreased(P<0.05).Compared with the normal control group,the expression of TLR4 protein in mPFC and hippocampus of the depression model group was significantly up-regulated(P<0.01).Compared with the control group,there was no statistically significant difference between the above indexes in the Model+TAK-242 group(P>0.05).Conclusions The depression rat model was successfully established by CUMS method.The function of Glu and GABA delivery system in mPFC and hippocampus of depression model rats was in disorder,and the expression of TLR4 protein was up-regulated,aggravating secondary brain injury.After the intervention of TAK-242,the above neurotransmitter abnormalities improved,the activation of TLR4 decreased,and the learning and memory function of the depressed rats improve

关 键 词：TOLL样受体4 抑郁症 谷氨酸 Γ-氨基丁酸 

分 类 号：R749.4[医药卫生—神经病学与精神病学]