颐脑解郁方对抑郁大鼠行为学和NLRP3相关炎性蛋白的影响  

Effect of Yinao Jieyu Formula on Behavior and NLRP3-related Inflammatory Proteins in Depressed Rats

作　　者：张双 李江林 赵瑞珍 张东枢 李骁群 唐启盛 ZHANG Shuang;LI Jianglin;ZHAO Ruizhen;ZHANG Dongshu;LI Xiaoqun;TANG Qisheng(Beijing University of Chinese Medicine,Beijing China 100029;The Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing China 100029)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学第三附属医院,北京100029

出　　处：《中医学报》2023年第10期2168-2174,共7页Acta Chinese Medicine

基　　金：中央高校基本科研业务费专项重点攻关项目(2020-JYB-ZDGG-144-3)。

摘　　要：目的:观察颐脑解郁方对抑郁大鼠行为学和NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)相关炎性蛋白的影响。方法:采用随机数字表法将32只雄性Wistar大鼠随机分为正常组、模型组、颐脑解郁方组(6.2 g·kg^(-1))和盐酸氟西汀组(2.3 g·kg^(-1)),每组8只。除正常组外,其余大鼠采用慢性不可预知温和刺激(chronic unpredictable mild stress,CUMS)法连续刺激21 d联合孤养法建立抑郁模型,并于应激结束后给予相应药物干预28 d,正常组和模型组灌胃等体积蒸馏水,灌胃体积均为10 mL·kg^(-1)。采用旷场实验和糖水偏好实验评估各组大鼠的行为学变化;ELISA法检测大鼠血清中白细胞介素-1β(interleukin 1β,IL-1β)、干扰素-γ(interferonγ,IFN-γ)的水平;RT-PCR检测海马和前额叶皮质组织中NLRP3 mRNA的表达量;Western Blot检测海马和前额叶皮质中NLRP3和gasdermin D(GSDMD)的蛋白表达水平。结果:与正常组比较,模型组大鼠糖水偏好率、活动总路程、水平运动得分和垂直运动得分显著降低,血清IL-1β、IFN-γ水平及海马和前额叶皮质中NLRP3 mRNA、NLRP3蛋白以及GSDMD蛋白表达水平显著升高;与模型组比较,颐脑解郁方组大鼠糖水偏好率、活动总路程、运动时间、水平运动得分和垂直运动得分显著升高,静止时间显著减少,血清IL-1β、IFN-γ水平及海马和前额叶皮质中NLRP3 mRNA、NLRP3蛋白以及GSDMD蛋白表达水平下降,差异均具有统计学意义(P<0.05)。结论:颐脑解郁方可能通过抑制海马和前额叶皮质中NLRP3的激活抑制下游GSDMD和炎症因子IL-1β、IFN-γ的成熟和释放,进而改善大鼠的抑郁样行为。Objective:To observe the effect of Yinao Jieyu formula on behavior and inflammatory protein related to NOD-like receptor thermoprotein domain related protein 3(NLRP3)in depressed rats.Methods:32 male Wistar rats were randomly divided into normal group,model group,Yinao Jieyu recipe group(6.2 g·kg^(-1))and fluoxetine hydrochloride group(2.3 g·kg^(-1)),with 8 rats in each group.Except for the normal group,the other rats used chronic unpredictable mildstress stimulation(CUMS)method to stimulate continuously for 21 days combined with solitary rearing method to establish the depression model,and gave corresponding drug intervention for 28 days after the stress ended.The normal group and the model group were given the same volume of distilled water by gavage,and the gavage volume was 10 mL·kg^(-1).The behavioral changes of rats in each group were evaluated by open field test and sugar water preference test.The levels of interleukin-1β(IL-1β)and-γ(interferonγ(IFN-γ))in serum of rats were detected by ELISA.RT-PCR was used to detect the expression of NLRP3mRNA in hippocampus and prefrontal cortex.WesternBlot was used to detect the protein expression levels of NLRP3 and gasderminD(GSDMD)in hippocampus and prefrontal cortex.Results:Compared with the normal group,the sugar water preference rate,total activity distance,horizontal exercise score and vertical exercise score of the model group decreased significantly,while the levels of IL-1β and IFN-γ in serum and the expression levels of NLRP3 mRNA,NLRP3 protein and GSDMD protein in hippocampus and prefrontal cortex increased significantly.Compared with the model group,the sugar water preference rate,total activity distance,exercise time,horizontal exercise score and vertical exercise score of rats in Yinao Jieyu recipe group were significantly increased,while the resting time was significantly decreased,while the levels of serum IL-1β and IFN-γ and the expression levels of NLRP3 mRNA,NLRP3 protein and GSDMD protein in hippocampus and prefrontal cortex were decreas

关 键 词：颐脑解郁方 抑郁症 NLRP3 GSDMD IL-1Β IFN-Γ 大鼠 

分 类 号：R285.5[医药卫生—中药学]