舍曲林在抑郁症大鼠模型抗抑郁中的作用及大鼠海马凋亡信号通路相关蛋白的差异性表达  

The role of sertraline in antidepressant of depression animal model and the differential expression of apoptosis signal pathway related protein in brain tissue

作　　者：王爱芹 褚延乐[2] 赵明军[1] 冯砚国[1] 张瑞岭[1] WANG Aiqin;CHU Yanle;ZHAO Mingjun;FENG Yanguo;ZHANG Ruiling(The Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453002,China;Pharmaceutical Department,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450014,China)

机构地区：[1]新乡医学院第二附属医院,河南新乡453002 [2]郑州大学第二附属医院药学部,郑州450014

出　　处：《河南大学学报（医学版）》2021年第1期1-6,共6页Journal of Henan University:Medical Science

基　　金：河南省高校科技创新团队支持计划(17IRTSTHN023)。

摘　　要：[目的]探讨舍曲林在抑郁症大鼠模型抗抑郁中的作用及大鼠海马凋亡信号通路相关蛋白表达水平的差异。[方法]选择54只健康成年雄性SD级大鼠为研究对象,随机数字表法随机分为对照组、模型组和舍曲林组,各18只。应用慢性不可预见性温和刺激(CUMS)法对模型组和舍曲林组建立抑郁症大鼠模型,对照组大鼠不给予处理。用Western blot法和qRT-PCR法检测各组大鼠海马B淋巴细胞瘤/白血病-2(Bcl-2)、Bcl-2的相关X蛋白(Bax)、半胱氨酸天冬氨酸蛋白酶(Caspase)-3、Caspase-9及Toll样受体4(TLR4)、MyD88蛋白含量及mRNA表达水平。[结果](1)对照组、模型组和舍曲林组建模前大鼠糖水偏好实验(SPT)偏好度、旷场实验(OFT)水平得分和垂直得分、鼠悬尾实验(TST)不动时间、强迫游泳测试实验(FST)不动时间比较差异均无统计学意义(P>0.05)。建模后模型组SPT偏好度显著降低,OBT水平运动得分和垂直运动得分均显著减小,FTST和FST不动时间均显著延长,与建模前比较差异均存在统计学意义(P<0.05),对照组上述行为学变化指标与建模前比较均无明显变化(P>0.05);建模后舍曲林组SPT偏好度、OBT水平运动得分和垂直运动得分及FTST和FST时间与模型组比较差异均有统计学意义(P<0.05)。(2)模型组大鼠海马CA1区锥体细胞肿胀、排列稀疏,细胞间隙增加,神经元数量减少,细胞胞浆中的尼氏体数量减少。舍曲林组大鼠海马CA1区神经元损伤表现相比模型组显著改善。(3)建模后模型组脑组织TLR4、MyD88及Bax、Caspase-3、Caspase-9蛋白含量和mRNA表达水平较建模前均明显升高,Bcl-2显著降低,而舍曲林组与模型组比较TLR4、MyD88及Bax、Caspase-3、Caspase-9蛋白含量和mRNA表达水平明显降低,Bcl-2则显著升高(P<0.05)。[结论]舍曲林能明显改善慢性应激抑郁症大鼠抑郁样行为,减轻大鼠神经元损伤和凋亡,其作用机制可能与其对凋亡信号通路Bax、Cas[Objective]To observe the antidepressant effect of sertraline and the difference of the expression level of apoptosis signal pathway related protein in hippocampus of depression rats.[Methods]54 healthy adult male SD rats were randomly divided into control group,model group and sertraline group,18 rats each.Chronic unpredictable mild stimulation(CUMS)was used to establish depression model in model group and sertraline group.Sertraline group rats were given intraperitoneal injection of sertraline.The behavioral changes of rats in each group were observed and detected.The apoptosis of hippocampal neurons was observed by Nissl staining.Western blot and qRT-PCR were used to detect Bcl-2,Bax,Caspase-3,caspase-9,toll like receptor4(TLR4),MyD88 protein content and mRNA expression level.[Results](1)After modeling,the SPT preference of the model group was significantly reduced,the horizontal and vertical movement scores of the OBT were significantly reduced,the TST time and FST time were significantly prolonged,and the difference was statistically significant(P<0.05).There were significant differences in SPT preference,OBT horizontal and vertical scores,FTST and FST time between the model group and sertraline group(P<0.05).(2)In the model group,the pyramidal cells in CA1 area of hippocampus were swollen and sparsely arranged,the intercellular space increased,the number of neurons decreased,and the number of Nissl bodies in the cytoplasm decreased.The damage of neurons in CA1 area of hippocampus in sertraline group was significantly improved compared with that in model group.(3)after modeling,TLR4,MyD88,Bax,Caspase-3,caspase-9 protein content and mRNA expression level in brain tissue of model group were significantly higher than those before modeling,and Bcl-2 was significantly lower,while TLR4,MyD88,Bax,Caspase-3,caspase-9 protein content and mRNA expression level were significantly lower in sertraline group compared with model group,while Bcl-2 was significantly higher(P<0.05).[Conclusion]Sertraline can significantly imp

关 键 词：慢性不可预见性刺激 抑郁 动物模型 神经元凋亡 舍曲林 

分 类 号：R749.05[医药卫生—神经病学与精神病学]