Cerebral Hemorrhage-Related Inflammatory Response Mediated by NINJ1 and the Protective Effects of Atorvastatin

Abstract

We investigated the relationship between NINJ1 and the inflammatory response in cerebral hemorrhage, as well as the relationship with the protective effects of atorvastatin. A cerebral hemorrhage model was constructed using injection of Type IV collagenase, and open field tests, Y-maze, and mNSS were used to evaluate the behavioral and neurological functions of mice. Enzyme-linked immunosorbent assays were used to detect the expression of tissue inflammatory factors. H&E and Nissl staining were used to detect tissue pathological changes. Western blotting was used to detect the relative expression levels of proteins. NINJ1 transgenic mice showed a more severe inflammatory response and neurological damage compared to wild-type mice, but intervention with NINJ1 monoclonal antibody Ab and atorvastatin could reduce the activation of NLRP3 mediated by NINJ1, decrease tissue inflammation, and, at the cellular level, atorvastatin could inhibit BV2 inflammation. IP experiment results showed that atorvastatin could interact with NINJ1 and inhibit its mediation of NLRP3 activation. Our research results show that NINJ1 in cerebral hemorrhage can promote the activation of NLRP3, further promoting neuroinflammation. Atorvastatin can interact with NINJ1, inhibiting its mediation of NLRP3 activation. NINJ1 is a new target for the treatment of cerebral hemorrhage, and we have revealed a new pharmacological mechanism and target for atorvastatin.