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Resveratrol alleviates vascular inflammatory injury by inhibiting inflammasome activation in rats with hypercholesterolemia and vitamin D2 treatment

Inflammation Research volume 64, pages 321–332 (2015)Cite this article

Abstract

Objective

Atherosclerosis (AS) is an inflammatory disease involved in vascular inflammatory injury. The inflammasome is an important part of inflammatory diseases and participates in the vascular inflammatory injury. Resveratrol (RSV) possesses anti-inflammatory activities, but its effects on inflammasomes during vascular injury remain unclear. This study focused on the effects and mechanisms of RSV on inflammasomes during vascular injury.

Methods

Male Sprague–Dawley rats were treated with a purified diet or cholesterol-enriched diet combined with vitamin D2 (VD; 1.8 million units/kg/days, Po) and saline or RSV (50 mg/kg/days, Po) daily for 5 weeks. The concentrations and enzyme activities of related indicators were measured by a spectrophotometer or ELISA kit. Their gene and protein expression levels were analyzed by reverse transcription–polymerase chain reaction and Western blot, respectively.

Results

Upon administration with RSV, rats with combined hyper cholesterol and VD demonstrated the following changes: the vascular histopathological changes were relieved, and the level of the von Willebrand factor decreased. The level of serum IL-1β, a marker of inflammasome activation, significantly decreased. The mRNA and protein expression levels of the three components of inflammasomes, namely, NOD-like receptor pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, and caspase-1, were downregulated. The effects of RSV were closely related to hypolipidemia (decrease in the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol combined with the expression of the lectin-like ox-LDL receptor and increase in high-density lipoprotein cholesterol), antioxidation (decrease in MDA levels and increase in SOD and GPx activities), and anti-inflammation (downregulation of the expression of IL-1β, intracellular adhesion molecule-1, and monocyte chemotactic protein-1). The mechanisms for the downregulation of NF-κB p65 and p38 MAPK expression, as well as the upregulation of SIRT1 expression, were analyzed.

Conclusion

This study proved that RSV inhibited inflammasome activation to protect vascular injury in vivo. RSV exhibited therapeutic potential in the treatment of vascular injury.

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Acknowledgments

This study was supported by the Zhejiang Province Welfare Research Technology Application (experimental animals) Project (No. 2014C37020).

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Zhejiang University of Technology, Hangzhou, 310004, Zhejiang, China

    Zu Yue Deng & Meng Mei Hu

  2. Zhejiang Institute for Food and Drug Control, Hangzhou, Zhejiang, China

    Zu Yue Deng & Meng Mei Hu

  3. State Key Laboratory of Safety Evaluation for New Drug, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China

    Yan Fei Xin & Chen Gang

Authors
  1. Zu Yue Deng
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Correspondence to Zu Yue Deng.

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Responsible Editor: Bernhard Gibbs.

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Deng, Z.Y., Hu, M.M., Xin, Y.F. et al. Resveratrol alleviates vascular inflammatory injury by inhibiting inflammasome activation in rats with hypercholesterolemia and vitamin D2 treatment. Inflamm. Res. 64, 321–332 (2015). https://doi.org/10.1007/s00011-015-0810-4

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  • DOI: https://doi.org/10.1007/s00011-015-0810-4

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