[1]康 涛,朱利娟,曹冰清,等.甲状腺激素受体β基因对β淀粉样蛋白42诱导的小胶质细胞炎症和细胞凋亡作用机制[J].陕西医学杂志,2021,50(10):1204-1209.[doi:DOI:10.3969/j.issn.1000-7377.2021.10.007]
　KANG Tao,ZHU Lijuan,CAO Bingqing,et al.Effect and mechanism of Thrb on microglia inflammation and apoptosis induced by Aβ42[J].,2021,50(10):1204-1209.[doi:DOI:10.3969/j.issn.1000-7377.2021.10.007]
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甲状腺激素受体β基因对β淀粉样蛋白42诱导的小胶质细胞炎症和细胞凋亡作用机制
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
50
期数:
2021年10期
页码:
1204-1209
栏目:
基础研究
出版日期:
2021-10-05

文章信息/Info

Title:
Effect and mechanism of Thrb on microglia inflammation and apoptosis induced by Aβ42
作者:
康 涛1; 朱利娟2; 曹冰清1; 薛延莉1; 杨 谦1
(1.陕西省人民医院神经内科,陕西 西安710068; 2陕西省人民医院麻醉科,陕西 西安710068)
Author(s):
KANG Tao; ZHU Lijuan; CAO Bingqing; XUE Yanli; YANG Qian
(Department of Neurology,Shaanxi Provincial People's Hospital,Xi'an 710068,China)
关键词:
甲状腺激素受体β基因;  阿尔兹海默症;  Sirt3/FOX3a;  细胞凋亡; 氧化应激
Keywords:
Thrb;  Alzheimer's disease;  Sirt3/FOX3a;  Apoptosis;  Oxidative stress
分类号:
R 392
DOI:
DOI:10.3969/j.issn.1000-7377.2021.10.007
文献标志码:
A
摘要:
目的:探究甲状腺激素受体β基因(Thrb)对β淀粉样蛋白42(Aβ42)诱导的小胶质细胞BV2炎症反应、氧化应激和凋亡的作用及作用机制。方法:RT-PCR和Western blot实验检测不同浓度的Aβ42对Thrb表达的影响; CCK-8实验检测Thrb对小胶质细胞BV2增殖的影响; V-FITC/PI检测Thrb对BV2细胞凋亡的影响; Western blot实验检测凋亡相关蛋白caspase-3和caspase-9的蛋白表达水平; 活性氧指示剂DCFH-DA检测活性氧(ROS)的水平。结果:Aβ42显著抑制Thrb表达且具有剂量依赖性(P<0.05); 过表达Thrb显著降低Aβ42诱导的小胶质细胞BV2的细胞凋亡率和炎症因子的水平(均P<0.05); 过表达Thrb显著缓解Aβ42诱导的小胶质细胞BV2的氧化应激(P<0.05); Thrb显著促进Sirt3和FOX3a的表达,相反,sh-Thrb显著抑制Sirt3和FOX3a的表达(均P<0.05); Sirt3/FOX3a通路参与Thrb对Aβ42诱导的细胞损伤的保护机制。结论:Thrb能够缓解Aβ42诱导的BV2细胞的氧化应激和凋亡,降低细胞损伤,其作用是通过调控Sirt3/FOX3a信号通路来实现的,这一结果能够为老年痴呆症的诊断和临床治疗提供分子基础。
Abstract:
bjective:To investigate the effect of Thrb on oxidative stress and apoptosis of Aβ42-induced microglia BV2 and the mechanism.Methods:RT-PCR and Western blot were used to detect different concentrations of Aβ42 on Thrb expression.CCK-8 assay was used to detect the effect of Thrb on the proliferation of microglia BV2.The effect of Thrb on BV2 cell apoptosis was detected by V-FITC/PI.Western blot was used to detect the protein expression of caspase-3 and caspase-9.The level of reactive oxygen species(ROS)was detected by DCFH-DA.Results:Aβ42 inhibited the expression of Thrb in a dose-dependent manner.Overexpression of Thrb significantly reduced the apoptosis rate and inflammatory factor level of Aβ42-induced microglia BV2,alleviated the oxidative stress of Aβ42-induced BV2(all P<0.05).Thrb significantly promoted the expression of Sirt3 and FOX3a,and sh-Thrb significantly inhibited Sirt3 and FOX3a expression(all P<0.05).Sirt3/FOX3a pathway involved in the protective mechanism of Thrb on Aβ42-induced cell injury.Conclusion:Thrb alleviates oxidative stress and apoptosis of microglia BV2,and reduces cell damage,which is achieved by regulating Sirt3/FOX3a signaling pathway.This result provides molecular basis for clinical treatment and diagnosis of Alzheimer's disease.

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更新日期/Last Update: 2021-10-08