Dexmedetomidine alleviates H₂O₂-induced oxidative stress and cell necroptosis through activating of α2-adrenoceptor in H9C2 cells

Oxidative stress induced necroptosis is important in myocardial ischemia/reperfusion injury. Dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, has protective effect on oxidative stress induced cell apoptosis, but effects of Dex and Dex-mediated α2-AR activation on oxidant induced necroptosis was unclear. H9C2 cardiomyocytes were pre-treated with or without Dex and α2-AR antagonist yohimbine hydrochloride (YOH) before being exposed to H₂O₂ to induce oxidative cellular damage. Cell viability and lactate dehydrogenase (LDH) were detected by ELISA kits, protein expressions of Heme Oxygenase 1(HO-1), receptor interacting protein kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3) were observed by WB, and TUNEL was used to detected cell apoptosis. H₂O₂ significantly decreased cell viability and increased LDH release and necroptotic and apoptotic cell deaths (all p < 0.05, H₂O₂ vs. Control). Dex preconditioning alleviated these injuries induced by H₂O₂. Dex preconditioning significantly increased expression of protein HO-1 and decreased expressions of proteins RIPK1 and RIPK3 induced by H₂O₂, while all these protective effects of Dex were reversed by YOH (all p < 0.05, Dex + H₂O₂ vs. H₂O₂; and YOH + Dex + H₂O₂ vs. Dex + H₂O₂). However, YOH did not prevent this protective effect of Dex against H₂O₂ induced apoptosis (YOH + Dex + H₂O₂ vs. Dex + H₂O₂, p > 0.05). These findings indicated that Dex attenuates H₂O₂ induced cardiomyocyte necroptotic and apoptotic cell death respectively dependently and independently of α2-AR activation.