APC Overexpression Suppresses the Pyroptosis of Subarachnoid Hemorrhage Model Cells through Regulating NLRP3 Inflammasome Pathway

Subarachnoid hemorrhage (SAH) is a kind of hemorrhagic stroke with high mortality. Activated protein C (APC) was implicated to play a neuroprotective role in central nervous system diseases. However, its role in SAH remains unclear. Our study aims to investigate the role of APC and its regulatory mechanism in SAH. The SAH rat model was constructed by internal carotid artery puncture. The SAH cell model was established by the application of oxygen hemoglobin. ELISA was performed to detect the level of cytokines. Flow cytometry was used to detect the population of pyroptosis cells. Neurological functions of rats were estimated using modified Garcia scoring and balance beam test. SAH hemorrhage was estimated using modified Sugawara's scoring. APC was significantly increased and NLRP3 was decreased in SAH rat model in a time-dependent manner. The application of APC recombinant protein 3K3A-APC could notably ameliorate SAH hemorrhage and improve neurological functions. Besides, 3K3A-APC could inhibit pyroptosis in a dose-dependent manner in SAH cell model. Moreover, the inhibition of NLRP3 could reverse the effects induced by the knockdown of APC. Our study revealed that APC could ameliorate SAH-induced EBI by suppressing pyroptosis via inhibiting NLRP3 inflammasome, which would provide a novel strategy for the treatment of SAH.