出 处:《时珍国医国药》2023年第11期2565-2569,共5页Lishizhen Medicine and Materia Medica Research
基 金:国家自然科学基金面上项目(81673843);山东省自然科学基金联合基金(ZR2022LZY016);国家中医药管理局全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号)。
摘 要:目的探究强志胶囊对CRS大鼠NF-κB/NLRP3炎症信号通路表达的影响,阐释强志胶囊对CRS大鼠神经炎症的作用机制。方法Wistar大鼠60只,雄性,SPF级,适应性饲养7天,根据糖水偏好实验及旷场实验的基线期数据将大鼠分为5组,即对照组(Control)、模型组(CRS)、强志组(CRS+Qiang-Zhi)、柴胡疏肝散组(CRS+Chai-Hu)、氟西汀组(CRS+fluoxetine)。采用CRS慢性束缚应激的方式制备抑郁模型大鼠。以体重、糖水偏好实验、旷场实验和水迷宫实验检测各组大鼠的行为学表型上的变化。以Elisa、Western-Blot、PCR检测各组大鼠血清和海马NF-κB/NLRP3炎症信号通路中相关炎症因子表达情况。结果(1)行为学实验结果:较CRS组相比,CRS+Qiang-Zhi组大鼠体重、糖水偏好指数、旷场实验中央区路程、旷场中央区停留时间及中央区进入次数显著提高(P<0.01;P<0.05;P<0.01;P<0.05;P<0.05)、水迷宫实验逃避潜伏期显著降低(P<0.01)、平台象限停留时间、平台象限路程、穿越平台次数等行为学指标显著提高(P<0.01;P<0.05;P<0.01);(2)Elisa结果显示,较CRS组大鼠相比,CRS+Qiang-Zhi组大鼠血清NF-κB、NLRP3、ASC、Caspase-1含量显著降低(P<0.01);(3)Western-Blot结果显示,较CRS组大鼠相比,CRS+Qiang-Zhi组大鼠海马NF-κB、NLRP3、ASC、Caspase-1含量显著降低(P<0.01;P<0.01;P<0.01;P<0.05);(4)PCR结果显示,较CRS组大鼠相比,CRS+Qiang-Zhi组大鼠血清NF-κB、NLRP3、ASC、Caspase-1mRNA表达显著降低(P<0.01;P<0.01;P<0.001;P<0.001)。结论(1)强志胶囊可以改善CRS抑郁模型大鼠的行为学表型和抑郁状态;(2)CRS抑郁模型大鼠的抑郁样行为发生过程中,海马脑区存在中枢神经炎症反应,强志胶囊可能通过下调NF-κB/NLRP3炎症信号通路相关蛋白及mRNA的表达从而发挥其抗抑郁作用。Objective To explore the effect of Qiangzhi capsule on the expression of NF-κB/NLRP3 inflammatory signal pathway in CRS rats,and explain the mechanism of Qiangzhi capsule on neuroinflammation in CRS rats.Methods Sixty wiatar rats,male,SPF grade.Adaptive feeding for 7 days.According to the baseline data of SPT sucrose experiment and OFT open field experiment,the experimental rats were divided into 5 groups,namely normal control group(control),CRS model group(CRS),Qiangzhi group(CRS+Qiang-Zhi),Chaihu Shugan powder group(CRS+Chai-Hu)and fluoxetine intervention group(CRS+fluoxetine).The depression model rats were made by CRS chronic restraint stress.The body weight,sugar preference test,open field test and Morris water maze test were used to detect the changes in the behavioral phenotype of rats in each group.ELISA,Western-Blot and PCR were used to detect the expression of related inflammatory factors in NF-κB/NLRP3 inflammatory signal pathway of different groups of experimental rats'serum and hippocampal.Results(1)The results of behavioral experiment showed that compared with the CRS group,the CRS+Qiang-zhi's body weight and sucrose preference index,center area distance and number of entries into the central area increased significantly of OFT(P<0.01;P<0.05;P<0.01;P<0.05;P<0.05),the escape latency decreased significantly of MWM(P<0.01)and the number of crossing the platform increased significantly of MWM(P<0.01;P<0.01;P<0.01),and there was no significant difference in each drug intervention group(P>0.05).(2)The results of ELISA showed that compared with the CRS group,the content of NF-κB,NLRP3,ASC and Caspase-1 in serum of CRS+Qiang-Zhi group decreased significantly(P<0.001).(3)The results of Western-Blot showed that compared with the CRS group rats,the content of NF-κB,NLRP3,ASC and Caspase-1 protein in hippocampus of CRS+Qiang-Zhi group decreased significantly(P<0.01;P<0.01;P<0.01;P<0.05).(4)The results of PCR showed that compared with the CRS group rats,the content of NF-κB,NLRP3,ASC and Caspase-1 mRNA in hi
关 键 词:抑郁症 海马 神经炎症 NF-κB/NLRP3信号通路
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