二氢杨梅素通过Sirt3抑制NLRP3炎性小体活性改善血管内皮细胞损伤

刘明华; 申卉; 汪小兰; 周曦; 张婷

doi:10.16016/j.2097-0927.202211043

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二氢杨梅素通过Sirt3抑制NLRP3炎性小体活性改善血管内皮细胞损伤

基础医学 | 更新时间：2026-01-09

- 二氢杨梅素通过Sirt3抑制NLRP3炎性小体活性改善血管内皮细胞损伤
- Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3
- 陆军军医大学学报 2023年45卷第9期页码：964-974
- 作者机构：
  
  400038 重庆, 陆军军医大学(第三军医大学)军事预防医学系军队营养与食品卫生学教研室, 重庆市营养与食品安全重点实验室, 重庆市医学营养研究中心
- 作者简介：
  
  [张婷，E-mail: t_zhang@hotmail.comZHANG Ting, E-mail: t_zhang@hotmail.com
- 基金信息：
  
  国家自然科学基金面上项目(81773409);重庆市自然科学基金一般项目(cstc2017jcyjAX0458)
- DOI：10.16016/j.2097-0927.202211043
  中图分类号： R151.2;R322.12;R329.25
- 收稿：2022-11-08，
  
  修回：2023-01-09，
  
  纸质出版：2023-05-15
- 稿件说明：
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刘明华, 申卉, 汪小兰, 等. 二氢杨梅素通过Sirt3抑制NLRP3炎性小体活性改善血管内皮细胞损伤[J]. 陆军军医大学学报, 2023,45(9):964-974.

Minghua LIU, Hui SHEN, Xiaolan WANG, et al. Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3[J]. Journal of Army Medical University, 2023, 45(9): 964-974.
刘明华, 申卉, 汪小兰, 等. 二氢杨梅素通过Sirt3抑制NLRP3炎性小体活性改善血管内皮细胞损伤[J]. 陆军军医大学学报, 2023,45(9):964-974. DOI： 10.16016/j.2097-0927.202211043.

Minghua LIU, Hui SHEN, Xiaolan WANG, et al. Dihydromyricetin ameliorates vascular endothelial damage by inhibiting NLRP3 inflammasome activity through Sirtuin 3[J]. Journal of Army Medical University, 2023, 45(9): 964-974. DOI： 10.16016/j.2097-0927.202211043.

摘要

目的

观察二氢杨梅素(dihydromyricetin

DHM)对通过Sirt3抑制棕榈酸诱导的血管内皮细胞NLRP3炎性小体活化

改善血管内皮细胞损伤的作用机制研究。

方法

棕榈酸(200 μmol/L)处理人脐静脉内皮细胞建立炎症损伤模型

不同浓度DHM (10、20、40 μmol/L)干预后检测内皮细胞活力、LDH释放水平以及内皮细胞黏附因子表达。运用qRT-PCR和蛋白免疫印迹法检测NLRP3炎性小体活化相关细胞因子的mRNA和蛋白表达水平。运用海马能量代谢检测平台和膜电位实验探索DHM对内皮细胞线粒体功能的调节作用。利用Sirt3特异性抑制剂3-TYP (50 μmol/L)和Sirt3过表达质粒干预

探索Sirt3在DHM抑制棕榈酸诱导NLRP3炎性小体活化中的作用。

结果

DHM能显著抑制棕榈酸诱导的内皮细胞活力下降、抑制LDH释放以及ICAM-1和VCAM-1的分泌(

0.05)。并且

DHM可显著改善线粒体呼吸耗氧量下降

ATP产量及剩余呼吸能力以及抑制线粒体膜电位升高(

0.05)。同时

DHM可以抑制棕榈酸诱导的NLRP3、IL-18和ASC等的mRNA和蛋白表达(

0.05)

Sirt3过表达质粒转染可增强DHM这一效应

而Sirt3抑制剂3-TYP处理则显著削弱DHM的作用。

结论

DHM通过激活Sirt3维持内皮细胞线粒体代谢

抑制NLRP3活化

减轻血管内皮细胞炎症损伤。

Abstract

Objective

To investigate the inhibitory effects and mechanism of dihydromyricetin (DHM) on the activation of NLRP3 inflammasome and improvement of palmitic acid induced injury in vascular endothelial cells through Sirtuin 3(Sirt3).

Methods

Human umbilical vein endothelial cells (HUVECs) were treated with palmitic acid (200 μmol/L) to establish an inflammatory injury model

which was subsequently intervened with different concentrations of DHM (10

20 and 40 μmol/L).Cell viability

LDH release level and expression of endothelial cell adhesion factors were detected respectively.qRT-PCR and Western blotting were used to measure the mRNA and protein levels of cytokines related to NLRP3 inflammasome activation.The regulatory effects of DHM on mitochondrial function of endothelial cells were determined by Seahorse Extracellular Flux Platform and mitochondrial membrane potential assay.Moreover

Sirt3-specific inhibitor 3-TYP (50 μmol/L) and Sirt3 overexpression plasmid were adopted to explore the role of Sirt3 in DHM inhibiting the activation of NLRP3 inflammasome induced by palmitic acid.

Results

DHM significantly inhibited the decline in cell viability

release of LDH

and secretion of endothelial cell adhesion factors ICAM-1 and VCAM-1 induced by palmitic acid (

0.05).Moreover

DHM remarkably improved the decrease of oxygen consumption for mitochondrial respiratory activity

enhanced ATP production and residual respiratory capacity

and suppressed the elevation of mitochondrial membrane potential (

0.05).Meanwhile

DHM also suppressed the mRNA and protein levels of NLRP3

IL-18 and ASC induced by palmitic acid (

0.05).Sirt3 overexpression enhanced the above effects of DHM

while the Sirt3 inhibitor 3-TYP obviously attenuated these effects.

Conclusion

DHM maintains mitochondrial metabolism of endothelial cells by activating Sirt3

inhibits the activation of NLRP3 inflammasome

and thus alleviates the inflammatory damage in HUVECs.

关键词

Keywords

references

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