PPARβ-related signal pathway involves in the effect of polydatin on high glucose-and insulin-induced cardiomyocyte hypertrophy / 中国药理学通报

ABSTRACT

Aim To investigate the effect of polydatin on cardiomyocyte hypertrophy induced by high glucose (25.5 mmol·L -1 )and insulin (0.1 μmol ·L -1 ) (HGI)and its possible influence on peroxisome prolif-erator-activated receptor-β (PPARβ)/nuclear tran-scription factor-κB (NF-κB)/nitric oxide (NO)signa-ling pathway.Methods The cardiomyocyte hypertro-phy was characterized in rat primary cardiomyocytes by measuring the cell surface area,protein content,and atrial natriuretic factor (ANF)mRNA expression.The mRNA and protein expressions were measured by qRT-PCR and Western blotting,respectively.The activity of NO synthase (NOS)and NO content were measured by reagent kit through ultraviolet spectroscopy.Results HGI significantly induced cardiomyocyte hypertrophy which increased the cell surface area,protein content and ANF mRNA expression (P <0.01 ).Meanwhile, the expressions of PPARβmRNA and protein reduced while the NF-κB p65 and iNOS expressions increased significantly which occurred in parallel with rising NOS activity and NO concentration (P <0.01 ).Polydatin (0.1,1,10 μmol·L -1 )inhibited the cardiomyocyte hypertrophy induced by HGI (P <0.01 ),and re-versed the mRNA and protein expressions of PPARβ, NF-κB p65 and iNOS,and NOS activity,as well as NO content.These effects of polydatin were abolished by GSK0660 (1 μmol·L -1 ),a selective PPARβan-tagonist (P <0.05 ).Conclusion Polydatin resists HGI-induced cardiomyocyte hypertrophy,which may be mediated by PPARβup-regulation,and then NF-κB-iNOS-NO pathway inactivation.