Protective Effect Of Ellagic Acid On Lipotoxic Injury In H9c2 Cardiomyocytes

Objective:To investigate the protective effect of ellagic acid（EA）on palmitate acid（PA）induced lipotoxic injury in H9c2 cardiomyocytes.Methods:H9c2 cardiomyocytes were pretreated with EA.The viability of H9c2cardiomyocytes was detected by MTT assay;MDA,SOD,ROS,TUNEL and JC-1 kits were used to detect the oxidative stress and apoptosis of cardiomyocytes;Western blot was used to detect the expression of endoplasmic reticulum stress pathway and apoptosis pathway related proteins.Results:（1）with the increase of PA concentration and time,the viability of H9c2cardiomyocytes decreased gradually in a concentration and time-dependent manner.After treated with 0.2 mmol·L^-1 PA for 24 h,the survival rate of cardiomyocytes decreased significantly（P<0.05）,the content of MDA increased significantly and the activity of SOD decreased significantly（P<0.05）.Therefore,PA concentration of 0.2 mmol·L^-1and action time of 24 h were selected as the optimal conditions for lipotoxicity modeling,and the follow-up experiments were continued.（2）When pretreated with different concentrations of EA,the survival rate of H9c2cardiomyocytes gradually increased in a concentration dependent manner.Compared with PA 0.2 mmol·L^-1group,EA 20μAfter pretreatment,the viability of cells began to increase significantly,the level of ROS in cells decreased significantly,the apoptosis of cells decreased significantly,the level of mitochondrial membrane potential increased significantly,and the cell morphology was close to normal.（3）PA could increase the expression levels of p-PERK、p-IRE1、GRP78、CHOP and Bax protein in H9c2 cardiomyocytes,and decrease the expression of Bcl-2 protein.Pretreatment with EA could significantly reverse these changes.Conclusion:PA can induce H9c2 cardiomyocytes apoptosis through endoplasmic reticulum stress mitochondrial apoptosis pathway,EA can significantly improve PA induced H9c2 cardiomyocytes lipotoxicity injury,and its specific mechanism may be related to the regulation of endoplasmic reticulum stress-mitochondrial apoptosis pathway.