首页|EGCG-PLGA纳米粒子减轻心肌缺血损伤的作用及机制研究

EGCG-PLGA纳米粒子减轻心肌缺血损伤的作用及机制研究

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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-P-NPs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.
The effect and mechanism of EGCG-PLGA nanoparticles on alleviating myocardial ischemic injury
Objective:To construct a drug delivery system of epigallocatechin gallate(EGCG)based on poly(lac-tic-co-glycolic acid)(PLGA)nanoparticles,and to study its effect and mechanism on myocardial ischaemic inju-ry.Methods:The preparation process of EGCG-PLGA nanoparticles(E-P-NPs)was improved,and the morpholo-gy of E-P-NPs was observed by transmission electron microscopy.The nanoparticles were characterised by mea-surement 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 car-diomyocytes 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 myocardi-al ischemic injury by inhibiting apoptosis and enable EGCG to better exert their efficacy.

epigallocatechin gallatepoly(lactic-co-glycolic acid)nanodrug delivery systemmyocardial isch-emic injury

李海琦、黄若晖、刘琦、简洁

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桂林医学院药学院,桂林 541199

岳阳市妇幼保健院,岳阳 414000

表没食子儿茶素没食子酸酯 聚乳酸—羟基乙酸共聚物 纳米药物递送系统 心肌缺血损伤

国家自然科学基金国家自然科学基金

8206065982360078

2024

广西医科大学学报
广西医科大学

广西医科大学学报

CSTPCD
影响因子:0.788
ISSN:1005-930X
年,卷(期):2024.41(3)
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