Activation of TGR5 with INT-777 attenuates oxidative stress and neuronal apoptosis via cAMP/PKCε/ALDH2 pathway after subarachnoid hemorrhage in rats.

摘要: Abstract Background Oxidative stress and neuronal apoptosis play important roles in the pathogenesis of early brain injury (EBI) after subarachnoid hemorrhage (SAH). The activation TGR5, a novel membrane-bound bile acid receptor, possesses anti-oxidative anti-apoptotic effects hepatobiliary disease kidney disease. present study aimed to explore neuroprotective effect TGR5 against EBI SAH potential underlying mechanisms. Methods endovascular perforation model was performed on 199 Sprague Dawley rats investigate beneficial SAH. INT-777, specific synthetic agonist, administered intranasally at 1 h induction. CRISPR ALDH2 were intracerebroventricularly 48 h before illuminate grade, short-term long-term neurobehavioral tests, TUNEL staining, Fluoro-Jade C Nissl immunofluorescence western blots 24 h Results expressions endogenous gradually increased peaked expressed primarily neurons, as well astrocytes microglia. with INT-777 significantly improved neurological deficits, accompanied by reduced oxidative Moreover, treatment cAMP, phosphorylated PKCe, ALDH2, HO-1, Bcl-2, while downregulated 4-HNE, Bax, Cleaved Caspase-3. abolished Conclusions In summary, attenuated via cAMP/PKCe/ALDH2 signaling pathway rats. Furthermore, may serve therapeutic target ameliorate