纳米载体介导的胎盘生长因子对大鼠急性心肌梗死后心脏功能的作用

摘要

Objective To explore the effect of placental growth factor(PGF) which by nanoparticle drug delivery system on rat cardiac function after acute myocardial infarction(AMI).Methods PGF were encapsulated in poly(lactic-co-glycolic acid) (PLGA) to form nanoparticles.All rats were divided into four groups with 10 in each group:Sham Group(normal rats),AMI Control Group(physiological saline were injected),PGF Group(PGF was injected),and PGF-PLGANPs Group(PGF-PL-GANPs was injected).Four weeks later,cardiac functions were evaluated by transthoracic echocardiography.The rats were sacrificed six weeks later,and the scar tissue of infracted area was analyzed with Masson trichrome analysis,and the expressions of TIMP-2,MT1-MMP and MMP-2 were evaluated by immunohistochemistry and western blot.Results PGF-PLGANPs were prepared successfully showing slow-release PGF for at least 15 days.Compared to AMI control group,PGF could improve cardiac function,inhibit the scar tissue area,and elevate the expression of TIMP-2,inhibit the expression of MT1-MMP and MMP-2,while PGF-PLGANPs showed better result than PGF (P ＜ 0.05).Conclusion Intramyocardial injection of PGF could improve the cardiac function after AMI in rats.The encapsulation of PGF in PLGA nanoparticles result in more significant efficacy compared to direct injection of PGF.%目的 探讨纳米载体缓释的胎盘生长因子(PGF)改善大鼠心肌梗死后心脏功能的作用及机制.方法 制备PGF纳米粒(PGF-PLGANPs),理化分析后行动物研究.40只大鼠急性心肌梗死(AMI)模型分为4组,每组10只,包括阴性对照组(未做手术处理),心肌梗死对照组(梗死区注射生理盐水30μl),PGF注射组(梗死区注射PGF溶液30μl,含2μg PGF),PGF-PLGANPs注射组(梗死区注射PGF-PLGANPs溶液30μl,含2μg PGF).术后4周行超声心动评估大鼠心功能,6周后处死,Masson法评价心脏瘢痕面积;免疫组化、蛋白免疫印迹检测心肌梗死组织中目的蛋白TIMP-2、MMP-2、MT1-MMP的表达水平.结果 成功制备了PGF-PLGANPs.术后4周超声心动结果显示,相较于阴性对照组,另外3组手术大鼠表现为不同程度心肌回声增强,左心室前壁变薄,收缩减弱等表现.PGF-PLGANPs注射组大鼠的左心室射血分数值、左心室短轴缩短率均显著高于PGF注射组和心肌梗死对照组,差异有统计学意义(P＜0.05).Masson染色结果显示,PGF干预可缩小AMI后心肌梗死面积,缓释递药的PGF-PL-GANPs注射组可获得更为显著的瘢痕面积改善(P＜0.05).结论 PGF干预AMI可显著改善大鼠心脏功能,纳米递药途径可获得更为良好的治疗效果.