Atorvastatin Inhibits High Glucose-induced Endoplasmic Reticulum Stress-induced Rat Cardiomyocyte Apoptosis

Objective Endoplasmic reticulum stress is involved in the pathophysiological processes of various diseases,and its effects are closely related to the activation of pathways,especially the PERK-eIF2? pathway.In recent years,several studies have shown that atorvastatin(ATV)has an inhibitory effect on apoptosis and may be related to endoplasmic reticulum stress,but the relevant pathway is still unclear.In this study,an endoplasmic reticulum stress model was established by culturing H9C2 rat cardiomyocytes with high glucose to observe the effect of endoplasmic reticulum stress on cardiomyocyte apoptosis.The effect of atorvastatin on endoplasmic reticulum stress and cardiomyocyte apoptosis and the influence of PERK-eIF2? pathway were further studied.This study provides a new experimental basis for understanding the anti-apoptotic effect of atorvastatin and the treatment of clinical coronary heart disease.Methods 1.H9C2 rat cardiomyocytes were cultured in DMEM medium with 10% fetal bovine serum and 1% penicillin streptomycin.The cultured cells were randomly divided into two groups,which were blank control group and high glucose group.The blank control group was cultured in DMEM medium,and the high glucose group was cultured in DMEM medium containing 17.6 mmol/L glucose.The relative survival rate of cells were detected by MTT assay and the expression levels of endoplasmic reticulum stress-related proteins GRP78 and PERK were detected by Western Blot at 0h,6h,12 h and 24 h.To observe whether high glucose can induce endoplasmic reticulum stress in H9C2 rat cardiomyocytes,leading to cardiomyocytes apoptosis.2.The previous experiment showed that high glucose induced endoplasmic reticulum stress in cardiomyocytes,leading to cardiomyocytes apoptosis.The expression levels of endoplasmic reticulum stress-related protein was up-regulated and the relative survival rate of cells decreased significantly at 24 h,so the time point was selected for 24 h in step2.H9C2 rat cardiomyocytes were cultured in DMEM medium with 10% fetal bovine serum and 1% penicillin streptomycin.To study the effect of atorvastatin on endoplasmic reticulum stress and cardiomyocyte apoptosis,the cultured cells were randomly divided into two groups,which were blank control group and model group.The model group were divided into three groups,which were high glucose group,high glucose+ATV group,high glucose+ salubrinal group(Sal group).High glucose+Sal group was positive control group.In order to investigate whether ATV or Salubrinal had an effect on endoplasmic reticulum stress in cardiomyocytes under normal culture conditions,ATV group or Sal group were set in addition to the blank control group.The relative survival rate of cells was detected by MTT assay,and the expression levels of PERK and eIF2? were detected by Western Blot.Results 1.There was no significant difference in GRP78 expression and PERK expression and the relative survival rate of cells between the high glucose 0h group and the blank control group.The high glucose 6h group,high glucose 12 h group or high glucose 24 h group was respectively compared with the blank control group,high glucose increased the expression levels of GRP78 and PERK and decreased the relative survival rate of cells.2.Compared with the blank control group,the expression levels of PERK and eIF2? of the high glucose group was increased,and the cell relative survival rate decreased.Compared with the high glucose group,PERK expression and eIF2? expression of the high glucose+ATV group decreased,and the cell relative survival rate increased.Compared with the high glucose group,eIF2? expression of the high glucose+Sal group decreased,and the cell relative survival rate increased.There was no significant difference in PERK expression.When the ATV group was compared with the blank control group or the Sal group was compared with the blank control group,ATV and Salubrinal had no significant difference in the relative survival rate of normally cultured cells and the expression levels of PERK and eIF2?.Conclusions High glucose can induce endoplasmic reticulum stress in rat cardiomyocytes,leading to cardiomyocyte apoptosis.Atorvastatin inhibits endoplasmic reticulum stress-induced apoptosis in rat cardiomyocytes,and its mechanism may be related to down-regulation of PERK-eIF2? pathway.