Vildagliptin Protects Palmitic Acid-induced Myocardial Inflammatory Damage in Diabetes Mellitus

OBJECTIVE To explore the mechanism of vildagliptin, a dipeptidyl peptidase 4 inhibitor(DPP-4i), in improving the inflammatory damage of cardiomyocytes induced by diabetes mellitus.

METHODS The AC16 cardiomyocytes cultured in vitro were randomly divided into blank group, palmitic acid(PA) group, 0.1, 1, 10 μmol·L⁻¹ vildagliptin group, and sitagliptin group (positive control group). The cell viability was detected by CCK-8 kit. The expressions of DPP-4, p-NF-κB and IκB were detected by Western blotting. The expression level of inflammatory cytokines TNF-α and IL-6 were detected by ELISA kit. TUNEL kit was used to detect cell apoptosis.

RESULTS After PA treatment, the cell morphology of AC16 human cardiomyocytes changed, CCK-8 results showed a decrease in cell survival rate, Western blotting results showed increased phosphorylation of NF-κB and increased expression of DPP-4 protein, and ELISA results showed increased expression level of inflammatory factors TNF-α and IL-6. The increase of TUNEL positive ratio promoted apoptosis of cardiomyocytes. After administration of DPP-4i vildagliptin, it could effectively inhibit the abnormal expression of DPP-4 protein induced by PA, improve the morphology of cardiomyocytes, and down-regulate the level of NF-κB phosphorylation. ELISA results showed that vildagliptin could improve the expression level of PA-induced inflammatory factors TNF-α and IL-6, and reduce the proportion of TUNEL positive(P<0.05).

CONCLUSION Vildagliptin can effectively antagonize PA-induced inflammatory injury of cardiomyocytes, antagonize myocardial injury induced by diabetic cardiomyopathy by inhibiting the phosphorylation level of NF-κB, reducing the expression level of intracellular inflammatory factors and inhibiting apoptosis.