Mechanism of Dexmedetomidine Alleviating Myocardial Ischemia-Reperfusion Injury Through Mitochondrial and ER Oxidative Stress Pathway

Abstract

Objective: To analyze the mechanism of dexmedetomidine through mitochondrial and ER oxidative stress pathway in neonatal rat cardiomyocytes. Methods: SD neonatal rats were selected as the research object, and the control group (Group A), H2O2 group (Group B), dexmedetomidine group (Group C) and dexmedetomidine + H2O2 group were constructed (Group D) four groups of neonatal rat cardiomyocyte oxidative injury models. After drug treatment, the morphology, LDH, GSH, ROS, casease-3,8,9 and 12 activities of neonatal rat cardiomyocytes were detected in turn. The mitochondrial membrane potential and apoptosis rate were detected by flow cytometry, and GRP78 and IRE1 were detected by Western blot α, Expression of Bcl-2 and Bax proteins. Results: 500umol/l was selected as the best reaction concentration of H2O2. H2O2 can cause the disorder of cytoskeleton sequencing and the disappearance of myocardial striations, while dexmedetomidine can reduce the damage of H2O2 to cardiomyocytes. Compared with group A, the activity levels of LDH and ROS in cardiomyocytes in group B increased significantly, and the activity level of GSH decreased significantly. Compared with group B, the activity of GSH in group D was significantly increased, while the activity of LDH and ROS decreased significantly. Compared with group A, the activity levels of Caspase-3,8,9 and 12 in cardiomyocytes of group B increased significantly. Compared with group B, the activity of Caspase-3,8,9 and 12 in cardiomyocytes in group D decreased significantly. The apoptosis rate of cardiomyocytes in group A was (18.36 ± 5.68)%, and that in group D was (39.64 ± 9.36)%. Compared with group A, the apoptosis rate in group B increased significantly; there was no significant change in the apoptosis rate in group C. Compared with group A, the ratio of Bax to Bcl-2 in group B increased significantly; compared with group B, the ratio of Bax to Bcl-2 in group D decreased significantly. Compared with group A, GRP78 and IRE1 α Significantly improved; Compared with group B, GRP78 and IRE1 in group D α Significantly reduced. Conclusion: Dexmedetomidine can inhibit the oxidative stress response and apoptosis induced by H2O2 in neonatal rat cardiomyocytes.