维格列汀对棕榈酸诱导糖尿病心肌炎性损伤的保护作用

Vildagliptin protects palmitic acid-induced myocardial inflammatory damage in diabetes mellitus

关键词:  DPP-4  维格列汀  糖尿病心肌病  棕榈酸  NF-κB  

Key words:  dipeptidyl peptidase 4  vildagliptin, diabetic cardiomyopathy  palmitic acid  NF-κB  

摘要:

摘要：目的 探究二肽基肽酶-4抑制剂（Dipeptidyl peptidase-4 inhibitors，DPP-4i）维格列汀改善糖尿病所诱导心肌细胞的炎性损伤作用机制。方法：CCK-8试剂盒检测细胞存活率；Western blot检测目的蛋白DPP-4、p-NF-κB、IκB的表达情况；Elisa试剂盒检测炎症因子TNF-α和IL-6表达水平；TUNEL试剂盒检测细胞凋亡情况等。结果：AC16人源心肌细胞经棕榈酸（Palmitic acid，PA）处理后，细胞形态改变，CCK-8结果显示细胞存活率下降，且Western blot结果显示NF-κB磷酸化增强并且DPP-4蛋白表达升高，Elisa结果显示炎症因子TNF-α和IL-6表达水平上升，TUNEL阳性比例增多促进心肌细胞凋亡。DPP-4i维格列汀给药后能够有效缓解PA诱导的心肌细胞形态改变，下调NF-κB磷酸化和DPP-4蛋白表达水平，Elisa结果显示维格列汀改善PA诱导炎症因子TNF-α和IL-6表达水平上升，及降低TUNEL阳性比例（p<0.05）。结论：本研究表明维格列汀可以有效拮抗PA诱导的心肌细胞炎性损伤，初步的机制研究表明，维格列汀可以通过抑制NF-κB磷酸化水平，降低胞内炎症因子表达水平与抑制细胞凋亡，从而拮抗DCM诱导心肌损伤。

Abstract:

ABSTRACT: 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 CCK-8 kit was used to detect cell survival rate. The expressions of DPP-4, p-NF-κB and IκB were detected by Western blot. The expression level of inflammatory cytokines TNF-α and IL-6 were detected by Elisa kit. TUNEL kit was used to detect cell apoptosis. RESULT After Palmitic acid (PA) treatment, the cell morphology of AC16 human cardiomyocytes changed, CCK-8 results showed a decrease in cell survival rate, Western blot 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 promotes apoptosis of cardiomyocytes. The administration of DPP-4 inhibitor vildagliptin can effectively alleviate PA-induced cardiac myocyte morphological changes, down-regulate the phosphorylation of NF-κB and the expression level of DPP-4 protein. Elisa results showed that vildagliptin can 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 This study shows that vildagliptin can effectively antagonize PA-induced inflammatory injury of cardiomyocytes. Preliminary mechanism studies indicate that vildagliptin can 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.