逍遥散对抑郁大鼠大脑皮层PERK、Caspase-12mRNA表达的影响  

Effects of Xiaoyaosan on the mRNA expression of PERK and Caspase-12 in the cerebral cortex of depressed rats

作　　者：冯向欣 何佩宜 陈聪 侯雅静 潘秋霞 陈家旭[4] FENG Xiangxin;HE Peiyi;CHEN Cong;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9期4377-4381,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);2021年贵州省大学生创新创业训练计划项目(No.202110662056);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蛋白激酶样内质网激酶(PERK)、含半胱氨酸的天冬氨酸蛋白水解酶-12(Caspase-12)mRNA表达水平,探讨逍遥散治疗抑郁症的相关分子机制。方法:将48只雄性SD大鼠随机分为正常组、模型组、逍遥散组、氟西汀组,每组12只。采用慢性束缚应激(CIS)方法制备抑郁大鼠模型,造模前30min给予相应药物灌胃治疗,持续21d。通过观察大鼠体质量、糖水消耗实验、旷场实验观察逍遥散对抑郁大鼠行为学改变的影响。常规HE染色法观察大鼠大脑皮层病理形态的改变。实时荧光定量PCR法检测各组大鼠大脑皮层内质网应激(ERS)信号分子PERK和Caspase-12 mRNA表达水平,酶联免疫法检测大鼠血清C反应蛋白(CRP)和核因子κB(NF-κB)的含量。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;使抑郁大鼠糖水消耗量与旷场实验中大鼠的直立次数、水平穿格数、修饰次数增加(P<0.01);改善抑郁大鼠大脑皮层病理结构;使大脑皮层PERK、Caspase-12 mRNA表达水平显著降低(P<0.01);血清CRP和NF-κB含量显著降低(P<0.01)。结论:逍遥散能改善慢性束缚应激大鼠抑郁状态,其机制可能与降低抑郁大鼠大脑皮层PERK、Caspase-12 mRNA表达水平,抑制ERS,进而保护大脑皮层组织细胞,发挥治疗抑郁症的作用。Objective:To observe the expression levels of PERK and Caspase-12 mRNA in the cerebral cortex of depressed rats,and to explore the molecular mechanism of Xiaoyaosan in the treatment of depression.Methods:Forty-eight male SD rats were randomly divided into:normal group,model group.Xiaoyaosan group,Fluoxetine group,12 rats in each group.Depressed rat models were prepared by chronic immobilization-stress(CIs),and rats were given corresponding drugs by gavage 30 minutes before modeling for 21 days.The effects of Xiaoyaosan on the behavioral changes of depressed rats were observed through rat body weight,sugar water consumption test and open field test.The pathological morphological changes of cerebral cortex were observed by routine HE staining.The mRNA expression levels of endoplasmic reticulum stress(ERS)signaling molecules PERK and Caspase-12 in the cerebral cortex of rats in each group were detected by real-time fluorescence quantitative PCR,and serum C-reactive protein(CRP)and nuclear factor-B(NF-xB)content were detected by enzyme-linked immunosorbent assay.Results:Compared with the model group,Xiaoyaosan group could effectively reduce the depression-like behavior of depressed rats,increase the number of sugar water consumption,the number of upright activity,the horizontal penetration and tidy hair number(P<0.01),the cerebral pathological structure of depression rats was improved,and the expression of PERK and Caspase-12 mRNA in the cerebral cortex were significantly decreased(Pc0.01),and the amount of serum CRP and NF-xB significantly decreased(P<0.01).Conclusion:Xiaoyaosan can improve the depression state of CIS rats,and its mechanism may be related to the protection of cerebral cortex tissue cells by reducing the mRNA expression levels of PERK and Caspase-12 in the cerebral cortex of depressed rats,and by inhibiting the occurrence of endoplasmic reticulum stress to play a role in the treatment of depression.

关 键 词：逍遥散 抑郁症 蛋白激酶样内质网激酶 含半胱氨酸的天冬氨酸蛋白水解酶-12 机制 内质网应激 C反应蛋白 核因子ΚB 

分 类 号：R285.5[医药卫生—中药学]