Protective effects of dexmedetomidine on hypoxia/reoxygenation injury in cardiomyocytes by regulating the CHOP signaling pathway.

Abstract

Hypoxia/reoxygenation (H/R) injury in myocardial cells occurs frequently during cardiac surgery and affects the prognosis of patients. The present study aimed to investigate the protective effects of dexmedetomidine (Dex) on H/R injury and its association with the C/EBP-homologous protein (CHOP) signaling pathway. An H/R model was constructed in H9C2 cells to investigate the effects of Dex on H/R injury. Cell viability, apoptosis and lactate dehydrogenase (LDH) levels were determined by MTT, flow cytometry and 2,4-dinitrophenylhydrazine colorimetric assays, respectively. The expression levels of inflammatory factors were measured by reverse transcription-quantitative PCR (RT-qPCR), and CHOP and glucose-regulated protein-78 (Grp78) expression levels were detected by RT-qPCR and western blotting. CHOP was overexpressed or knocked down to detect the cell viability, apoptosis, LDH level and the expression levels of inflammatory factors and Grp78. The results demonstrated that in the H/R group, cell viability was lower and apoptosis was higher, and that higher levels of LDH and inflammatory factors were present compared with those in the Dex+H/R group. Silencing of CHOP significantly reversed the H/R-reduced cell viability, high apoptotic rate and LDH levels, as well as the elevated expression levels of inflammatory factors and Grp78 caused by H/R injury, whereas the overexpression of CHOP inhibited cell viability and promoted apoptosis, elevated LDH level and expression of inflammatory factors and Grp78 compared with the negative control. Additionally, pretreatment with Dex significantly alleviated the H/R injury; thus, Dex may protect H9C2 cells against H/R induced cell injury, possibly by suppressing the CHOP signaling pathway.