Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney

Frontiers in Surgery

卷:8

Weifeng Liu¹  Xiaoyi Shi²  Shengli Cao²  Peihao Wen²  Jiakai Zhang²  Bowen Hu²  Zhihui Wang²  Dongjing Yang⁴  Jihua Shi⁴  Wenzhi Guo⁴  Shuijun Zhang⁴ 

[1] Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang, China;

[2] Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;

[3] Henan Engineering Technology Research Center of Organ Transplantation, Zhengzhou, China;

[4] Zheng Zhou Key Laboratory of Hepatobiliary and Pancreatic Diseases and Organ Transplantation, Zhengzhou, China;

关键词: brain death;    renal injury;    pyroptosis;    caspase-1;    caspase-11;    hypoxia;   

DOI  :  10.3389/fsurg.2021.760989

来源: DOAJ

【 摘 要 】

Brain death (BD) induces an organ-level inflammatory response. However, the underlying mechanisms have not been fully elucidated. Here, we investigated the role of caspase-1-mediated pyroptosis in BD-induced kidney injury in rats. A BD model was established in Sprague-Dawley rats. The rats were intravenously injected with Z-YVAD-FMK 1 h before BD, and sham-operated rats served as controls. After 0, 1, 2, 4, and 6 h of BD, renal injury, and renal expression of the nod-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, caspase-11, gasdermin D (GSDMD), IL-1β, and IL-18 were assessed using quantitative reverse transcriptase-polymerase chain reaction, western blotting, and immunohistochemistry. Blood urea nitrogen and serum creatinine levels were measured. Additionally, renal tubular epithelial cells (NRK-52E) were subjected to 3 h of hypoxia followed by 6 h of reoxygenation and incubated with Z-YVAD-FMK before hypoxia and reoxygenation. Caspase-11 was knocked-down using small interfering RNA technology. Cell viability and levels of pyroptosis-associated proteins were assessed thereafter. NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 expression levels were upregulated in BD rats. Treatment with Z-YVAD-FMK reduced mRNA and protein levels of caspase-1, GSDMD, IL-1β, and IL-18, improved renal function, and alleviated renal injury. Z-YVAD-FMK efficaciously reduced pyroptosis effects in kidneys in BD rats. Thus, it could be considered as a therapeutic target for BD-induced kidney injury.

【 授权许可】

Unknown