Activated protein C overexpression suppresses the pyroptosis of subarachnoid hemorrhage model cells by regulating the NLRP3 inflammasome pathway

Yan,Ai; Pan,Xuyan; Wen,Xianqiang; Nie,Xiaohu; Li,Yuntao

doi:10.3892/etm.2021.10827

Activated protein C overexpression suppresses the pyroptosis of subarachnoid hemorrhage model cells by regulating the NLRP3 inflammasome pathway

Authors:
- Ai Yan
- Xuyan Pan
- Xianqiang Wen
- Xiaohu Nie
- Yuntao Li
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Affiliations: Department of Neurosurgery, Huzhou Central Hospital, Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang 313000, P.R. China
Published online on: September 30, 2021 https://doi.org/10.3892/etm.2021.10827
Article Number: 1391
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Subarachnoid hemorrhage (SAH) is a condition with a high associated mortality rate that is caused by hemorrhagic stroke. Activated protein C (APC) serves a neuroprotective role in central nervous system diseases. However, its role in SAH remains unclear. The present study aimed to investigate the role of APC and its regulatory mechanism in SAH. The SAH rat model was constructed through internal carotid artery puncture, while the SAH cell model was established via the application of oxygenated hemoglobin. ELISA was performed to detect the level of cytokines, and flow cytometry was used to determine the population of pyroptotic cells. Reverse transcription‑quantitative PCR and western blotting were used to examine the relative mRNA and protein levels of APC. APC was silenced using specific APC short hairpin RNA. Neurological functions of rats were estimated using modified Garcia scoring and the balance beam test, while SAH was estimated using modified Sugawara's scoring. The results demonstrated that the expression of APC was significantly decreased, whereas the expression of NLR family pyrin domain‑containing 3 (NLRP3) was increased in the SAH rat model in a time‑dependent manner. The application of APC recombinant protein 3K3A‑APC could significantly ameliorate SAH and improve neurological functions. In addition, 3K3A‑APC could inhibit pyroptosis in a dose‑dependent manner in the SAH cell model. Moreover, the NLRP3 inhibitor BAY11‑7082 could reverse the upregulation of pyroptosis induced by APC‑knockdown. Overall, the present study revealed that APC could ameliorate SAH‑induced early brain injury by suppressing pyroptosis via inhibition of the NLRP3 inflammasome, which could provide a novel strategy for the treatment of SAH.

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