基于Nrf2/HO-1信号通路介导的炎症反应探讨天智颗粒对血管性痴呆大鼠神经炎症的影响  

Effect of Tianzhi granule on neuroinflammation in rats with vascular dementia based on inflammatory response mediated by Nrf2/HO-1 signaling pathway

作　　者：廖玲 郑文 张元亚 黄晨 刘娜 杨丽华 余鸿博 LIAO Ling;ZHENG Wen;ZHANG Yuanya;HUANG Chen;LIU Na;YANG Lihua;YU Hongbo(Department of General Medicine,Shangrao People's Hospital,Shangrao 334000,China;Department of Neurology,Shangrao People's Hospital,Shangrao 334000,China;Department of Pathology,Shangrao People's Hospital,Shangrao 334000,China;Department of Clinical Laboratory,Shangrao People's Hospital,Shangrao 334000,China)

机构地区：[1]上饶市人民医院全科医学科,上饶334000 [2]上饶市人民医院神经内科,上饶334000 [3]上饶市人民医院病理科,上饶334000 [4]上饶市人民医院检验科,上饶334000

出　　处：《中国免疫学杂志》2025年第4期815-821,827,共8页Chinese Journal of Immunology

基　　金：江西省卫生健康委科技计划项目(202312277)。

摘　　要：目的:探究天智颗粒对血管性痴呆(VD)大鼠神经炎症的抑制作用。方法:60只大鼠随机分为假手术组(Sham)、模型组(VD)、天智颗粒低剂量组(TZG-L)、天智颗粒高剂量组(TZG-H),每组15只。采用双侧颈总动脉闭塞构建VD大鼠模型,Sham组不结扎。TZG-L组、TZG-H组每天灌胃天智颗粒5 g/kg、20 g/kg,Sham组、VD组灌胃等量生理盐水,持续8周。Y电迷宫实验检测大鼠认知能力;尼氏染色、FJC染色检测神经元损伤;TUNEL染色检测神经元凋亡;免疫荧光染色和Western blot检测颞叶皮层组织Bcl-2、Bax、Caspase-3、NLRP3、ASC、Caspase-1、IL-1β、IL-18、TNF-α、Iba-1、GFAP、MPO、Nrf2、HO-1蛋白水平。PC12细胞分为对照组(Control)、谷氨酸组(Glutamate)、TZG-L组和TZG-H组。采用谷氨酸(20μmol/L)构建神经元损伤模型,TZG-L组、TZG-H组加入天智颗粒1 mg/ml、4 mg/ml。各组细胞孵育48 h,CCK8法和TUNEL染色检测细胞活性及凋亡;免疫荧光染色和Western blot检测细胞Bcl-2、Bax、Caspase-3、Nrf2、HO-1蛋白水平。结果:与Sham组相比,VD组大鼠认知能力降低,神经元TUNEL阳性细胞比例增加,Bcl-2水平降低,Bax、Caspase-3、NLRP3、ASC、Caspase-1、IL-1β、IL-18、TNF-α、Iba-1、GFAP、MPO、Nrf2、HO-1水平升高(均P<0.05)。与VD组相比,TZG-L组、TZG-H组大鼠认知能力升高,神经元TUNEL阳性细胞比例减少,Bcl-2、Nrf2、HO-1水平升高,Bax、Caspase-3、NLRP3、ASC、Caspase-1、IL-1β、IL-18、TNF-α、GFAP、Iba-1、MPO水平降低(均P<0.05)。Control组神经元形态正常;与Control组相比,Glutamate组神经元细胞变形,神经元活性降低,凋亡率升高,Bcl-2水平降低,Bax、Caspase-3、Nrf2、HO-1水平升高(均P<0.05)。与Glutamate组相比,TZG-L组、TZG-H组细胞损伤减轻,神经元活性升高,凋亡率减少,Bcl-2、Nrf2、HO-1水平升高,Bax、Caspase-3水平降低(均P<0.05)。结论:天智颗粒能够抑制VD大鼠神经元凋亡和NLRP3炎症小体表达,抑制小胶质细胞/星形胶质�Objective:To explore inhibitory effect of Tianzhi granule on neuroinflammation in vascular dementia(VD)rats.Methods:Sixty rats were randomly divided into Sham group,VD group,TZG-L group and TZG-H group,with 15 rats in each group.Bilateral common carotid artery occlusion was used to construct VD rats model,Sham group was not ligated.Rats in TZG-L group and TZG-H group were gavaged with Tianzhi granule 5 g/kg,20 g/kg every day,while rats in Sham group and VD group were gavaged with same amount of normal saline for 8 weeks.Y-maze test was used to detect cognitive ability of rats;Nissl staining and FJC staining were used to assess neuronal damage;TUNEL staining was used to detect neuronal apoptosis;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 protein levels in temporal cortex tissue.PC12 cells was divided into Control group,Glutamate group,TZG-L group and TZG-H group.Glutamate(20μmol/L)was used to construct neuron injury model.TZG-L group and TZG-H group were added with Tianzhi granule 1 mg/ml,4 mg/ml.Neurons in each group were incubated for 48 h.CCK8 method and TUNEL staining were used to detect activity and apoptosis of neurons;immunofluorescence staining and Western blot were used to detect Bcl-2,Bax,Caspase-3,Nrf2,HO-1 protein levels in cells.Results:Compared with Sham group,cognitive ability of rats in VD group were decreased,TUNEL positive neurons ratio was increased,Bcl-2 level was decreased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO,Nrf2,HO-1 levels were increased(all P<0.05).Compared with VD group,cognitive ability of rats in TZG-L group and TZG-H group were increased,TUNEL positive neurons ratio was decreased,Bcl-2,Nrf2,HO-1 levels were increased,Bax,Caspase-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,TNF-α,Iba-1,GFAP,MPO levels were decreased(all P<0.05).Morphology of neurons in control group were normal;compared with control group,neurons in Glutamate group were swollen,activity of n

关 键 词：天智颗粒 血管性痴呆 神经炎症 Nrf2/HO-1信号通路 

分 类 号：R749.13[医药卫生—神经病学与精神病学]