肝X受体激动剂通过激活SIRT1信号级联改善Aβ诱导的视网膜色素上皮细胞炎症和凋亡反应

甘敏; 周巧雅; 洪美静; 李雪; 彭惠

doi:10.16016/j.1000-5404.202003092

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肝X受体激动剂通过激活SIRT1信号级联改善Aβ诱导的视网膜色素上皮细胞炎症和凋亡反应

神经科学 | 更新时间：2026-01-09

- 肝X受体激动剂通过激活SIRT1信号级联改善Aβ诱导的视网膜色素上皮细胞炎症和凋亡反应
- Liver X receptor agonist ameliorates amyloid β-induced inflammation and apoptosis in retinal pigment epithelial cells by activating SIRT1 signaling cascade
- 第三军医大学学报 2020年42卷第14期页码：1398-1406
- 作者机构：
  
  400016 重庆，重庆医科大学附属第一医院眼科，眼科学重庆市市级重点实验室，重庆市眼科研究所
- 作者简介：
  
  [彭惠, E-mail:pengh9@sina.comPENG Hui, E-mail: pengh9@sina.com
- 基金信息：
  
  国家自然科学基金面上项目(81670881)
- DOI：10.16016/j.1000-5404.202003092
  中图分类号： R329.25;R774.5;R977.6
- 收稿：2020-03-10，
  
  修回：2020-04-30，
  
  纸质出版：2020-07-30
- 稿件说明：
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甘敏, 周巧雅, 洪美静, 等. 肝X受体激动剂通过激活SIRT1信号级联改善Aβ诱导的视网膜色素上皮细胞炎症和凋亡反应[J]. 第三军医大学学报, 2020,42(14):1398-1406.

Min GAN, Qiaoya ZHOU, Meijing HONG, et al. Liver X receptor agonist ameliorates amyloid β-induced inflammation and apoptosis in retinal pigment epithelial cells by activating SIRT1 signaling cascade[J]. Journal of Third Military Medical University, 2020, 42(14): 1398-1406.
甘敏, 周巧雅, 洪美静, 等. 肝X受体激动剂通过激活SIRT1信号级联改善Aβ诱导的视网膜色素上皮细胞炎症和凋亡反应[J]. 第三军医大学学报, 2020,42(14):1398-1406. DOI： 10.16016/j.1000-5404.202003092.

Min GAN, Qiaoya ZHOU, Meijing HONG, et al. Liver X receptor agonist ameliorates amyloid β-induced inflammation and apoptosis in retinal pigment epithelial cells by activating SIRT1 signaling cascade[J]. Journal of Third Military Medical University, 2020, 42(14): 1398-1406. DOI： 10.16016/j.1000-5404.202003092.

摘要

目的

探讨LXR-SIRT1调控轴在淀粉样β(amyloidβ

Aβ)诱导的视网膜上皮(retinal pigment epithelial

RPE)细胞炎症和凋亡中的作用。

方法

体外培养ARPE-19细胞系，收集湿性年龄相关性黄斑变性(age-related macular degeneration，AMD)患者和正常受试者的人外周血单个核细胞(human peripheral blood mononuclear cell

PBMC)并检测其中沉默信息调节因子1(silencing information regulator 1

SIRT1)的mRNA表达。用1.0、5.0 μmol/L的Aβ1-40和5.0 μmol/L Aβ40-1处理ARPE-19细胞24 h，Real-time PCR检测SIRT1、IL-1β、p21在ARPE-19细胞中的表达，探讨Aβ对ARPE-19细胞炎症、凋亡的影响。用5.0 μmol/L Aβ1-40和5.0 μmol/L TO90处理ARPE-19细胞，Western blot检测SIRT1、LXRα、ace-NF-κB、NF-κB、ace-p53、p53、p21的表达，研究Aβ1-40刺激及TO90预处理对SIRT1信号级联的影响。在敲低SIRT1后，Western blot检测NF-κB和p53信号通路的表达，进一步验证TO90对SIRT1信号级联的调控作用。

结果

SIRT1在湿性AMD患者的PBMC中明显下调(

0.01)。Aβ1-40刺激ARPE-19细胞后，SIRT1在mRNA及蛋白水平明显下调(

0.05)，p21在mRNA及蛋白水平明显上调(

0.05)，IL-1β在基因水平明显上调(

0.05)，ace-NF-κB、NF-κB、ace-p53、p53在蛋白水平显著上调(

0.05)，而TO90预处理则可逆转Aβ1-40对这些因子的调节(

0.05)。SIRT1敲低后，TO90对ace-NF-κB、NF-κB、ace-p53、p53上调的逆转作用显著下降(

0.05)。

结论

LXR激动剂通过激活SIRT1信号级联改善Aβ诱导的ARPE-19细胞炎症及凋亡反应。

Abstract

Objective

To investigate the role of liver X receptor (LXR)-SIRT1 regulatory axis in inflammation and apoptosis of retinal pigment epithelial (RPE) cells induced by β-amyloid (Aβ).

Methods

Human peripheral blood mononuclear cells (PBMCs) were collected from patients with wet age-related macular degeneration (AMD) and normal subjects for detection of SIRT1 mRNA expression. And then

human RPE cell line ARPE-19 stimulated with 1.0

5.0 μmol/L Aβ1-40 or 5.0 μmol/L Aβ40-1 was examined for expression of SIRT1

IL-1β and p21 using real-time PCR to investigate the effects of Aβ on cell inflammation and apoptosis; Subsequently

the expression levels of SIRT1

LXRα

ace-NF-κB

NF-κB

ace-p53

p53

and p21 proteins in ARPE-19 cells treated with 5.0 μmol/L Aβ1-40

5.0 μmol/L TO90

or both were detected using Western blotting to analyze the effect of Aβ1-40 stimulation and TO90 pretreatment on SIRT1 signaling cascade. Finally

after knocking down SIRT1

the expression of NF-κB and p53 signaling pathways was detected by Western blot analysis to further verify the regulatory effect of TO90 on the SIRT1 signaling cascade.

Results

SIRT1 was significantly down-regulated in the PBMCs of patients with wet AMD (

0.05). Aβ stimulation of ARPE-19 cells caused obvious downregulation of SIRT1 (

0.05) and upregulation of p21 at both the mRNA and protein levels (

0.05)

upregulation of IL-1β at the mRNA level (

0.05)

and upregulation of ace-NF-κB

NF-κB

ace-p53

and p53 at the protein level (

0.05); TO90 pret

reatment effectively abolished the effects of Aβ on these factors (

0.05). After SIRT1 knockdown

the reverse effect of TO90 on the upregulation of ace-NF-κB

NF-κB

ace-p53

and p53 was significantly reduced (

0.05).

Conclusion

LXR agonists improve Aβ-induced inflammation and apoptosis in ARPE-19 cells by activating the SIRT1 signaling cascade.

关键词

Keywords

references

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