首页|维格列汀对棕榈酸诱导糖尿病心肌炎性损伤的保护作用

维格列汀对棕榈酸诱导糖尿病心肌炎性损伤的保护作用

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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诱导心肌细胞的炎性损伤作用机制。方法 体外培养AC16心肌细胞随机分为空白组、棕榈酸(palmitic acid,PA)组、0。1、1。、10 μmol-L-1维格列汀组以及西格列汀组(阳性对照组)。采用CCK-8试剂盒检测细胞存活率;Western blotting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。结果 AC16人源心肌细胞经PA处理后,细胞形态改变;CCK-8结果显示细胞存活率下降;Western blotting结果显示NF-κB磷酸化增强,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。维格列汀给药后能有效抑制PA诱导的DPP-4蛋白异常表达,改善心肌细胞形态,并下调NF-κB磷酸化水平。ELISA结果显示维格列汀改善PA诱导的炎症因子TNF-α和IL-6表达水平上升,降低TUNEL阳性比例(P<0。05)。结论 维格列汀可以有效拮抗PA诱导的心肌细胞炎性损伤,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,从而拮抗糖尿病心肌病诱导的心肌损伤。
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 AC 16 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 AC 16 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.

dipeptidyl peptidase-4vildagliptindiabetic cardiomyopathypalmitic acidNF-κB

杨瑞南、于莹、秦侃

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安徽医科大学药学院,合肥 230061

安徽医科大学第三附属医院药学部,合肥 230061

二肽基肽酶-4 维格列汀 糖尿病心肌病 棕榈酸 NF-κB

安徽省医疗卫生重点专科建设项目安徽医科大学校科研基金项目

皖卫函[2021]273号2022xkj104

2024

中国现代应用药学
中国药学会

中国现代应用药学

CSTPCD北大核心
影响因子:0.877
ISSN:1007-7693
年,卷(期):2024.41(11)
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