Mechanism underlying mitigation of remifentanil postconditioning-induced protection of diabetic cardiomyocytes: the relationship with histone deacetylase 3 expression / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the relationship between histone deacetylase 3 (HDAC3) expression and the mechanism underlying mitigation of remifentanil postconditioning-induced protection of diabetic cardiomyocytes.Methods H9c2 cells were cultured in DMEM/F12 culture medium supplemented with 10％ fetal bovine serum.The cells were seeded in 6-well plates (2 ml/well) at a density of 105 cells/ml.After the cells were cultured for 12 h,the cells were attached to the wall and cultured for 48 h in the normoglycemic (5.5 mmol/L) or hyperglycemic (25 mmol/L) DMEM culture medium.The cells were then randomly divided into 6 groups (n =18 each) using a random number tablecontrol group (group CON),hypoxia/reoxygenation group (group H/R),remifentanil postconditioning group (group RPC),hyperglycemia group (group HG),hyperglycemia plus hypoxia/reoxygenation group (group HG-H/R),and hyperglycemia plus remifentanil postconditioning group (group HG-RPC).In H/R,RPC,HG-H/R and HG-RPC groups,the cells were exposed to 95％ N2-5％ CO2 in an incubator for 5 h after changing the culture medium for Tyrode solution.In H/R and HG-H/R groups,the culture medium was changed to the DMEM/F12 culture medium supplemented with 10％ fetal bovine serum and glucose at the corresponding concentration,and the cells were then incubated for 1 h.In RPC and HG-RPC groups,the cells were incubated in the DMEM culture medium containing remifentanil at the final concentration of 1 μmol/L,and the cells were then incubated for 1 h.At 1 h of reoxygenation,the cell viability was measured by CCK-8 assay,the cell apoptosis was detected by AnnexinV-FITC/PI flow cytometry,and the expression of HDAC3 and caspase-3 in cells was detected by Western blot.The apoptotic rate was calculated.Results Compared with group CON,the cell viability was significantly decreased,the cell apoptotic rate was significantly increased,and the expression of caspase-3 and HDAC3 was significantly up-regulated in group H/R (P＜ 0.05).Compared with group H/R,the cell viability was significantly increased,the apoptotic rate was significantly decreased,and the expression of caspase-3 and HDAC3 was significantly down-regulated in group RPC (P＜0.05).Compared with group HG,the cell viability was significantly decreased,the apoptotic rate was significantly increased,and the expression of cspase-3 and HDAC3 was significantly up-regulated in group HG-H/R (P＜0.05).There was no significant difference in the parameters mentioned above between group HG-RPC and group HG-H/R (P＞0.05).Conclusion The mechanism underlying mitigation of remifentanil postconditioning-induced protection of diabetic cardiomyocytes is associated with hyperglycemia-induced up-regulation of HDAC3 expression.