李海琦, 黄若晖, 刘琦, 简洁. EGCG-PLGA纳米粒子减轻心肌缺血损伤的作用及机制研究[J]. 广西医科大学学报, 2024, 41(3): 406-412. DOI: 10.16190/j.cnki.45-1211/r.2024.03.012
引用本文: 李海琦, 黄若晖, 刘琦, 简洁. EGCG-PLGA纳米粒子减轻心肌缺血损伤的作用及机制研究[J]. 广西医科大学学报, 2024, 41(3): 406-412. DOI: 10.16190/j.cnki.45-1211/r.2024.03.012
LI Haiqi, HUANG Ruohui, LIU qi, JIAN jie. The effect and mechanism of EGCG-PLGA nanoparticles on alleviating myocardial ischemic injury[J]. Journal of Guangxi Medical University, 2024, 41(3): 406-412. DOI: 10.16190/j.cnki.45-1211/r.2024.03.012
Citation: LI Haiqi, HUANG Ruohui, LIU qi, JIAN jie. The effect and mechanism of EGCG-PLGA nanoparticles on alleviating myocardial ischemic injury[J]. Journal of Guangxi Medical University, 2024, 41(3): 406-412. DOI: 10.16190/j.cnki.45-1211/r.2024.03.012

EGCG-PLGA纳米粒子减轻心肌缺血损伤的作用及机制研究

The effect and mechanism of EGCG-PLGA nanoparticles on alleviating myocardial ischemic injury

  • 摘要: 目的:构建基于聚乳酸-羟基乙酸共聚物(PLGA)纳米粒子的表没食子儿茶素没食子酸酯(EGCG)药物递送系统,研究其对心肌缺血损伤的作用及机制。方法:改进现有EGCG-PLGA纳米粒子(E-P-NPs)制备工艺,以透射电镜观察所制备的E-PNPs形态,并测量聚合物分散性指数、Zeta电位、纳米粒径和载药率,进行纳米粒表征;以荧光标记法观察心肌细胞对纳米粒子的摄取情况。体外建立心肌细胞缺氧模型,体内建立小鼠急性心肌缺血损伤模型,检测不同浓度E-P-NPs对细胞活力、细胞凋亡、心肌肌钙蛋白(I cTn-I)水平及Bcl-2、Caspase9、Bax表达的影响。结果:E-P-NPs呈圆球形,多分散性指数(PDI)为0.285,平均粒径193.5 nm,电位-28.7 mV,载药率9.23%,可被心肌细胞摄取。体内、外实验研究均表明,E-P-NPs可剂量依赖性地增强心肌细胞活力,降低cTn-I水平,降低凋亡率,上调Bcl-2蛋白表达,下调Caspase9、Bax蛋白表达,抑制细胞凋亡;E-P-NPs对缺血心肌的保护作用优于 EGCG。结论:E-P-NPs 粒径分布较集中,均一性较好,可通过抑制凋亡减轻心肌缺血损伤,且能使EGCG更好地发挥药效。

     

    Abstract: Objective:To construct a drug delivery system of epigallocatechin gallate (EGCG) based on poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and to study its effect and mechanism on myocardial ischaemic injury. Methods:The preparation process of EGCG-PLGA nanoparticles (E-P-NPs) was improved, and the morphology of E-P-NPs was observed by transmission electron microscopy. The nanoparticles were characterised by measurement of polymer dispersibility index (PDI), zeta potential, nanoparticle size and drug loading rate. The uptake of nanoparticles by cardiomyocytes was observed using fluorescent labelling method. The hypoxia model of cardiomyocytes in vitro and acute myocardial infarction injury model in vivo were established. The effects of EGCG and E-P-NPs with different concentrations on cell viability, level of cardiac troponin I (cTn-I), apoptosis rate as well as levels of Bcl-2, Caspase9 and Bax were detected. Results:The E-P-NPs were spherical in shape, PDI was 0.285, the average particle size was 193.5 nm, the potential was -28.7 mV, and the drug loading rate was 9.23%. The nanoparticles could be taken up by cardiomyocytes. Both in vivo and in vitro experimental studies showed that E-P-NPs dose-dependently could enhance the viability of cardiomyocytes, decrease the level of cTn-I and apoptosis rate, up-regulate the Bcl-2 protein expression, down-regulate the Caspase9 and Bax protein expression, and inhibit the apoptosis. The protective effect of E-P-NPs on ischemic myocardia was better than that of EGCG. Conclusion:E-P-NPs, with concentrated particle size distribution and good homogeneity, can alleviate myocardial ischemic injury by inhibiting apoptosis and enable EGCG to better exert their efficacy.

     

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