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

Exp Ther Med. 2021 Dec;22(6):1391. doi: 10.3892/etm.2021.10827. Epub 2021 Sep 30.ABSTRACTSubarachnoid 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...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Authors: Source Type: research

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Source: Frontiers in Neurology - Category: Neurology Source Type: research
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