达格列净减轻氧化低密度脂蛋白诱导的内皮细胞焦亡和功能障碍  

Dapagliflozin attenuates endothelial cell pyroptosis and dysfunction induced by oxidized low-density lipoprotein

作　　者：赵权威 李辉 刘大男 龚才伟 陈龙 Zhao Quanwei;Li Hui;Liu Danan;Gong Caiwei;Chen Long(Department of Cardiology,Affiliated Hospital of Guizhou Medical University,Institute of Medical Sciences,Guizhou Medical University,Guiyang 550004,Guizhou Province,China)

机构地区：[1]贵州医科大学附属医院心血管内科,贵州医科大学医学科学研究所,贵州省贵阳市550004

出　　处：《中国组织工程研究》2024年第1期80-85,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81660083),项目负责人:刘大男;贵州省科技创新人才团队项目[(2020)5014],项目负责人:刘大男;贵州省“百”层次创新型人才培养计划项目[(2015)4026],项目负责人:刘大男。

摘　　要：背景:达格列净是钠-葡萄糖共转运蛋白2的抑制剂,可以通过调节糖代谢和抑制炎症改善内皮细胞功能,从而延缓动脉粥样硬化的进展。目的:观察达格列净对氧化低密度脂蛋白诱导的内皮细胞焦亡和内皮功能障碍的影响。方法:将人脐静脉内皮细胞分为3组:对照组不进行任何干预,模型组加入氧化低密度脂蛋白处理24 h,达格列净组在加入氧化低密度脂蛋白的基础上给予达格列净干预24 h,CCK-8检测内皮细胞增殖活性,ELISA检测细胞培养上清液中细胞间黏附分子1、血管细胞黏附分子1和单核细胞趋化蛋白1水平;硝酸还原酶法检测细胞一氧化氮水平;Hoechst 33342/PI荧光双染和乳酸脱氢酶释放实验检测内皮细胞焦亡情况和焦亡特征;Western blot检测内皮细胞焦亡因子NLRP3、caspase-1、GSDMD、白细胞介素18和白细胞介素1β蛋白表达。结果与结论:①氧化低密度脂蛋白可以导致内皮细胞焦亡和功能障碍;②与对照组相比,模型组细胞活性和一氧化氮水平下降(P<0.05),而乳酸脱氢酶、细胞间黏附分子1、血管细胞黏附分子1以及单核细胞趋化蛋白1显著增多(P<0.05);与模型组相比,达格列净组细胞活性和一氧化氮水平明显增加(P<0.05),而乳酸脱氢酶、细胞间黏附分子1、血管细胞黏附分子1以及单核细胞趋化蛋白1显著下降(P<0.05);③与模型组相比,达格列净组细胞焦亡率以及焦亡因子NLRP3、caspase-1、GSDMD、白细胞介素18和白细胞介素1β蛋白表达明显减少(P<0.05);④以上结果表明,达格列净可以抑制氧化低密度脂蛋白诱导的内皮细胞焦亡并改善内皮细胞功能障碍。BACKGROUND:Dapagliflozin,an inhibitor of sodium-glucose cotransporter 2,can delay the progression of atherosclerosis by regulating glucose metabolism,inhibiting inflammation and improving endothelial cell function.OBJECTIVE:To study the effect of dapagliflozin on cell pyroptosis and endothelial dysfunction induced by oxidized low-density lipoprotein.METHODS:Human umbilical vein endothelial cells were divided into a control group(no intervention),a model group(treated with oxidized low-density lipoprotein for 24 hours),and a dapagliflozin group(treated with oxidized low-density lipoprotein+dapagliflozin for 24 hours).Endothelial cell proliferation activity was measured by cell counting kit-8 assay.The levels of intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 in cell supernatant were detected using ELISA.Nitric oxide level in the cells was detected by nitrate reductase assay.The pyroptosis rate and characteristics of endothelial cells were detected by Hoechst 33342/PI fluorescence co-staining and lactate dehydrogenase release assay.The protein expression levels of NLRP3,caspase-1,GSDMD,interleukin-1β,and interleukin-18 were detected by western blot assay.RESULTS AND CONCLUSION:(1)Oxidized low-density lipoprotein could cause pyroptosis and dysfunction of endothelial cells.(2)Compared with the control group,the level of nitric oxide and cell activity were decreased(P<0.05),while lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly increased in the model group(P<0.05).Compared with the model group,cell activity and nitric oxide levels significantly increased(P<0.05),but lactate dehydrogenase,intercellular adhesion molecule 1,vascular cell adhesion molecule 1,and monocyte chemotactic protein-1 levels were significantly diminished in the dapagliflozin group(P<0.05).(3)Compared with the model group,cell pyroptosis rate and the protein expression of pyroptosis factor NLR

关 键 词：达格列净 焦亡 氧化低密度脂蛋白 NLRP3炎症小体 人脐静脉内皮细胞 内皮细胞功能 动脉粥样硬化 

分 类 号：R459.9[医药卫生—治疗学] R313[医药卫生—临床医学] R543