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VX765，一种特异性半胱氨酸天冬氨酸蛋白酶-1 抑制剂，通过抑制内皮细胞焦亡和屏障功能障碍缓解肺缺血再灌注损伤。

VX765, a Specific Caspase-1 Inhibitor, Alleviates Lung Ischemia Reperfusion Injury by Suppressing Endothelial Pyroptosis and Barrier Dysfunction.

机构信息

Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning, 530021 Guangxi Zhuang Autonomous Region, China.

Key Laboratory for Basic Science and Prevention of Perioperative Organ Dysfunction, Guangxi Medical University Cancer Hospital, Nanning, 530021 Guangxi Zhuang Autonomous Region, China.

出版信息

Biomed Res Int. 2021 Dec 22;2021:4525988. doi: 10.1155/2021/4525988. eCollection 2021.

DOI:10.1155/2021/4525988
PMID:34977239
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8716216/
Abstract

Lung ischemia reperfusion injury (LIRI) is a complex pathophysiological process with high morbidity and mortality. An important pathophysiological characteristic of LIRI is endothelial barrier dysfunction, although the mechanism involved in this process remains unclear. VX765, a specific caspase-1 inhibitor, has been shown to have a protective effect against several diseases including sepsis, atherosclerosis, and glial inflammatory disease. The objective of this study was to determine whether VX765 had a protective effect in LIRI. The results showed that lung ischemia/reperfusion (I/R) and oxygen/glucose deprivation and reoxygenation (OGD/R) induced endothelial pyroptosis and barrier dysfunction characterized by an inflammatory response. Treatment with VX765 successfully alleviated I/R- and OGD/R-induced endothelial pyroptosis and barrier dysfunction by inhibiting caspase-1 and . In conclusion, these findings showed that VX765 provided effective protection against lung I/R-induced endothelial pyroptosis and barrier dysfunction.

摘要

肺缺血再灌注损伤（LIRI）是一种具有高发病率和死亡率的复杂病理生理过程。LIRI 的一个重要病理生理特征是内皮屏障功能障碍，尽管其涉及的机制尚不清楚。VX765 是一种特定的半胱氨酸天冬氨酸蛋白酶-1（caspase-1）抑制剂，已被证明对包括脓毒症、动脉粥样硬化和神经胶质炎症性疾病在内的多种疾病具有保护作用。本研究旨在确定 VX765 是否对 LIRI 具有保护作用。结果表明，肺缺血/再灌注（I/R）和氧/葡萄糖剥夺及再氧合（OGD/R）诱导内皮细胞焦亡和以炎症反应为特征的屏障功能障碍。用 VX765 治疗成功地通过抑制半胱氨酸天冬氨酸蛋白酶-1（caspase-1）和炎性体激活来缓解 I/R 和 OGD/R 诱导的内皮细胞焦亡和屏障功能障碍。总之，这些发现表明，VX765 对肺 I/R 诱导的内皮细胞焦亡和屏障功能障碍提供了有效的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/e4a8b003ede6/BMRI2021-4525988.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/e2d7df750fbc/BMRI2021-4525988.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/afc73dcc7b46/BMRI2021-4525988.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/2cb0a46ddf22/BMRI2021-4525988.004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/251fcad5bde3/BMRI2021-4525988.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/f576c0f18835/BMRI2021-4525988.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/8287a8a2d659/BMRI2021-4525988.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/e4a8b003ede6/BMRI2021-4525988.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/e2d7df750fbc/BMRI2021-4525988.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/e91565965219/BMRI2021-4525988.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/afc73dcc7b46/BMRI2021-4525988.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/2cb0a46ddf22/BMRI2021-4525988.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/e4d6a6866cbe/BMRI2021-4525988.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/251fcad5bde3/BMRI2021-4525988.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/f576c0f18835/BMRI2021-4525988.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/8287a8a2d659/BMRI2021-4525988.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/faaa/8716216/e4a8b003ede6/BMRI2021-4525988.009.jpg

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