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Gastrodin ameliorates microvascular reperfusion injury–induced pyroptosis by regulating the NLRP3/caspase-1 pathway

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Abstract

Inflammation is a pivotal feature of myocardial reperfusion–induced microvascular injury and dysfunction. However, the molecular mechanisms by which myocardial reperfusion triggered inflammation remain incurable. The NLRP3 inflammasome is a key intracellular sensor that detection of cellular stress to activation of caspase-1, and consequent IL-1β maturation and pyroptotic cell death. Here, we showed that NLRP3 inflammasome played a key role in myocardial reperfusion–induced microvascular injury. We observed NLRP3 inflammasome activation and pyroptosis in both cardiac microvascular endothelial cells and myocardial I/R animal model. Gastrodin, an effective monomeric component extracted from the herb Gastrodia elata BIume, blocked cardiac microvascular endothelial cell pyroptosis via inhibiting NLRP3/caspase-1 pathway. Gastrodin also reduced interleukin-1β (IL-1β) production in vivo and in vitro. Furthermore, gastrodin treatment attenuated infarct size and inflammatory cells infiltration and increased capillary formation. Gastrodin is thus a potential therapeutic for NLRP3-associated inflammatory disease.

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Funding

This work was supported in part by the National Natural Science Foundation of China (grant no. 31760292; grant no. 81760087; grant no. 81560050) and the Department of Science and Technology of Yunnan Province (grant no. 2017FA035; grant no. 2017FE467 (-008), Provincial major sepcial projects (grant no.2019ZF011-2) and the Program for Innovative Research Team (in Science and Technology) in the University of Yunnan Province.

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Author notes

  1. Hongquan Lu contributed equally to this work and should be considered joint first author.

Authors and Affiliations

  1. Biomedical Engineering Research Center, Kunming Medical University, 1168 West Chunrong Road, Yuhua Avenue, Chenggong District, Kunming, 650500, Yunnan, China

    Wenjing Sun, Hongquan Lu, Lechun Lyu, Ling Li & Di Lu

  2. Department of Nuclear Medicine, Third People’s Hospital of Honghe State, Honghe, 661000, China

    Hongquan Lu

  3. Department of Technology Transfer Center, Kunming Medical University, Kunming, 650500, China

    Lechun Lyu & Di Lu

  4. Department of Anatomy and Histology, School of Basic Medical Sciences, Kunming Medical University, Kunming, 650500, China

    Ping Yang

  5. Department of Cardiology, The Second Affiliated Hospital, Kunming Medical University, Kunming, 650501, China

    Zhi Lin & Lin Sun

  6. The Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Road, Wuhua District, Kunming, 650101, China

    Lin Sun

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  1. Wenjing Sun
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Correspondence to Lin Sun or Di Lu.

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All animal experimental protocols were reviewed and approved by the Ethics Committee of Kunming Medical University for the use of laboratory animals.

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Sun, W., Lu, H., Lyu, L. et al. Gastrodin ameliorates microvascular reperfusion injury–induced pyroptosis by regulating the NLRP3/caspase-1 pathway. J Physiol Biochem 75, 531–547 (2019). https://doi.org/10.1007/s13105-019-00702-7

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