逍遥散对抑郁大鼠大脑皮层NLRP3信号通路和凋亡分子的影响  

Effects of Xiaoyaosan on NLRP3 signaling pathway and apoptotic molecules in the cerebral cortex of depressed rats

作　　者：陈聪 周静 侯雅静 潘秋霞 陈家旭[4] CHEN Cong;ZHOU Jing;HOU Yajing;PAN Qiuxia;CHEN Jiaxu(Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Inner Mongolia Medical University,Hohhot 010110,China;Special Medical Center of PLA Strategic Support Force,Beijing 100101,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]贵州中医药大学,贵阳550025 [2]内蒙古医科大学,呼和浩特010110 [3]中国人民解放军战略支援部队特色医学中心,北京100101 [4]北京中医药大学,北京100029

出　　处：《中华中医药杂志》2023年第11期5203-5207,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81630104,No.82104852);内蒙古自治区自然科学基金项目(No.2022QN08009);内蒙古医科大学面上项目(No.YKD2022MS064);2021年度中心第二批博士毕业生科研启动基金项目(No.21ZX16)。

摘　　要：目的:观察抑郁大鼠大脑皮层NLRP3信号通路和凋亡分子的变化,探讨逍遥散在治疗抑郁症方面相关的分子机制。方法:将60只雄性SD大鼠随机分为正常组、模型组、逍遥散组、氟西汀组、MCC950组。采用慢性束缚应激(CIS)的方法制备抑郁大鼠模型,造模前30 min给予相应药物灌胃治疗,持续21 d。通过糖水消耗实验、旷场实验、强迫游泳实验观察逍遥散对抑郁大鼠行为学改变的影响。实时荧光定量PCR法检测大鼠大脑皮层凋亡分子的mRNA表达水平,免疫组织化学法检测NLRP3信号通路蛋白的表达。结果:与模型组比较,逍遥散组可有效减轻抑郁大鼠的抑郁样行为,使得抑郁大鼠糖水消耗率与旷场实验中大鼠的运动总距离、中央区停留时间增加,缩短强迫游泳累计不动时间,降低抑郁大鼠大脑皮层凋亡分子的mRNA表达水平,降低大脑皮层NLRP3信号通路蛋白的表达水平(P<0.01);改善抑郁大鼠大脑皮层病理结构。结论:逍遥散对抑郁大鼠的作用效果明显,通过调节大鼠大脑皮层NLRP3信号通路而发挥抗抑郁作用。Objective:To observe the changes in NLRP3 signaling pathway and apoptotic molecules in the cerebral cortex of depressed rats,and to explore the molecular mechanisms of Xiaoyaosan in the treatment of depression.Methods:Sixty SD male rats were randomly divided into normal group,model group,Xiaoyaosan group,Fluoxetine group,and MCC950 group.A depressed rat model was prepared by chronic immobilization stress(CIS)and treated with drags 30 min before moldulation for 21 days.The effect of Xiaoyaosan on behavioral changes in depressed rats were observed by sugar water consumption,open field test and forced swimming.The mRNA expression levels of apoptotic molecules in each rat cerebral cortex were determined by real-time PCR and the expression of NLRP3 signaling proteins by immunohistochemistry.Results:Compared with the model group,Xiaoyaosan group could effectively reduce the depression-like behavior of depressed rats,increase the sugar water consumption rate of depressed rats and the total exercise distance and central residence time of rats in open field experiment,shorten the accumulated immobility time of forced swimming,and reduce the mRNA expression level of apoptosis molecules in the cerebral cortex of depressed rats,the expression level of NLRP3 signaling pathway protein in cerebral cortex was decreased(P<0.01):The pathological structure of cerebral cortex in depressed rats was improved.Conclusion:Xiaoyaosan has obvious effect on depressed rats and exerted antidepressant effects by regulating the NLRP3 signaling pathway in the rat cerebral cortex.

关 键 词：逍遥散 抑郁症 NLRP3 Caspase-1 白细胞介素-1β GRP78 CHOP CASPASE-12 

分 类 号：R285.5[医药卫生—中药学]