Hyperbaric oxygen via mediating SIRT1‐induced deacetylation of HMGB1 improved cReperfusion inj/reperfusion injury

Ischemic stroke leads to severe neurological dysfunction in adults. Hyperbaric oxygen (HBO) induces tolerance to cReperfusion inj/reperfusion (I/R) injury. Therefore, our aims were to investigate whether SIRT1 participates in regulatingin the neuro‐protective effect of HBO in a cerebral I/R model and its mechanism. Mice N2a cells were used to construct an oxygen deprivation/reperfusion (OGD/R) model to simulate in vitro brain I/R injury and to evaluate the role of HBO in OGD/R stimulated cells. Cell proliferation was detected using MTT, and apoptosis was determined by flow cytometry. ELISA was used to measure the concentration of TNF‐α, IL‐1β and IL‐6 related inflammatory factors. RT‐qPCR and western blot assays were performed to test the expression of SIRT1. Immunoprecipitation was used to detect acetylation of HMGB1. Expression of SIRT1 was obviously reduced after OGD/R treatment in N2a cells, while SIRT1 was obviously enhanced in HBO treated cells. Moreover, knockdown of SIRT1 induced neuro‐inflammation damage in cells and HBO effectively improved the inflammatory response in OGD/R treated cells by affecting SIRT1 levels. Furthermore, HBO induced the deacetylation of HMGB1 via regulating SIRT1. Interestingly, HBO via regulating the SIRT1‐induced HMGB1 deacetylation and suppressing MMP‐9 improved ischemic brain injury. HBO regulated ischemic brain injury via regulation of SIRT1‐induced HMGB1 deacetylation, making it a potential treatment for ischemic brain injury treatment. After ischemia/reperfusion treatment, the expression of SIRT1 in N2a cells was significantly reduced, and the expression of SIRT1 in HBO‐treated cells increased. HBO induced the deacetylation of HMGB1 by regulating SIRT1 and localized HMGB1 in the nucleus. HBO could also improve ischemic brain injury by regulating SIRT1‐induced deacetylation of HMGB1 and inhibiting MMP‐9.