Protective Effect of Liraglutide on Hypoxia and High Glucose-induced Oxidative Stress Injury in Cardiomyocyte / 中国药师

ABSTRACT

Objective:To explore the effects and possible mechanism of liraglutide on hypoxia and high glucose-induced oxidative stress injury in cardiomyocytes. Methods:The neonatal rat cardiomyocytes were separated and cultured in vitro. The hypoxia and high glucose-induced injury model was established in neonatal rat cardiomyocytes. The cells were divided into six groupsthe normal control group, liraglutide control group, hypoxia and high glucose model group, liraglutide treatment group, GLP-1R antagonist group and hyperosmotic control group. The metabolic ability of the cells was detected by MTT assay, the activities of LDH and CK-MB were detected by colorimetric method,SOD activity and MDA content were determined by xanthine oxidase method and thiobarbituric acid method,ROS level was measured by chemiluminescence method. The mRNA and protein expression of adaptor protein p66Shc was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Results:Compared with those in the normal control group, the cells in hypoxia and high glucose model group had poorly metabolic ability,the content of LDH, CK-MB, MDA and ROS increased (P < 0.01), the activity of SOD decreased (P <0.01), and the expression of adaptor protein p66Shc greatly increased(P <0.01). After the treatment with liraglutide,the above mentioned parameters were all improved(P < 0.01). Exendin(9-39),an antagonist of GLP-1R,attenuated the protective effect of liraglutide. Conclusion:Liraglutide has a protective effect on cardiomyocytes by down-regulating adaptor protein p66Shc expression and reducing ROS formation.