RvD1binding with FPR2 attenuates inflammation via Rac1/NOX2 pathway after neonatal hypoxic-ischemic injury in rats.

摘要: Abstract Neuroinflammation plays a crucial role in the pathological development after neonatal hypoxia-ischemia (HI). Resolvin D1 (RvD1), an agonist of formyl peptide receptor 2 (FPR2), has been shown to exert anti-inflammatory effects many diseases. The objective this study was explore protective RvD1 through reducing inflammation HI and contribution Ras-related C3 botulinum toxin substrate 1 (Rac1)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) pathways RvD1-mediated protection. Rat pups (10-day old) were subjected or sham surgery. administrated by intraperitoneal injection 1 h HI. FPR2 small interfering ribonucleic acid (siRNA) Rac1 activation CRISPR administered prior treatment elucidate possible mechanisms. Time course expression Western blot ELISA conducted at 6 h, 12 h, 24 h, 48 h 72 h post Infarction area, short-term neurological deficits, immunofluorescent staining 24 h Long-term behaviors evaluated 4 weeks Endogenous levels decreased time dependent manner while increased HI, peaking Activation FPR2, with RvD1, reduced percent infarction alleviated short- long-term deficits. Administration attenuated while, either inhibition siRNA reversed those effects. Our results showed that neuroinflammation which then interacted Rac1/NOX2 signaling pathway, thereby area alleviating deficits rat pups. may be potential therapeutic approach reduce