负载血管生成素1的聚乳酸羟基乙酸-聚乙二醇纳米微粒促进大鼠心肌梗死后心肌修复

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (8): 1114-1120.

负载血管生成素1的聚乳酸羟基乙酸-聚乙二醇纳米微粒促进大鼠心肌梗死后心肌修复

方涛¹, 杨婉浠¹, 李昕¹, 丛志成¹, 张沛宗¹, 祁泉², 宋兵^2*

兰州大学 1.第一临床医学院; 2.第一医院心血管外科,甘肃兰州 730000

收稿日期:2020-09-21 修回日期:2021-01-04 出版日期:2021-08-05 发布日期:2021-07-21
通讯作者: *hnfangss@163.com
基金资助:
甘肃省自然科学基金(18JR3RA349);兰州大学第一医院院内基金(ldyyyn2019-04);甘肃省卫生行业科研计划项目(GSWSKY2020-49,GSWSKY2018-49)

Poly (lactic-co-glycolic acid)-poly (ethylene glycol) scaffold incorporating angiopoietin 1 loaded nanoparticles promotes cardiac repair after myocardial infarction in rats

FANG Tao¹, YANG Wan-xi¹, LI Xin¹, CONG Zhi-cheng¹, ZHANG Pei-zong¹, QI Quan², SONG Bing^2*

1. the First Clinical Medical College,Lanzhou University,2.Department of Cardiovascular Surgery,the First Hospital,Lanzhou University,Lanzhou 730000, China

Received:2020-09-21 Revised:2021-01-04 Online:2021-08-05 Published:2021-07-21
Contact: *hnfangss@163.com

摘要/Abstract

摘要： 目的研究负载血管生成素1(Ang1)的聚乳酸羟基乙酸(PLGA)-聚乙二醇(PEG)纳米微粒(Ang1-PLGA-PEG)对心肌梗死(MI)后心肌修复的作用,并研究其作用于心肌梗死后心肌修复的作用机制。方法复制大鼠心肌梗死模型,1 周后,将大鼠随机分为模型组(心肌梗死周围区域注射100 μL PBS溶液)(n=8)、Ang1组[注射含Ang1的PBS溶液(100 μL,25 ng/μL)](n=8)、Ang1-PLGA-PEG组[注射100 μL纳米微粒混悬液,约含(1.61±0.05)μg Ang1](n=9)。4 周后,进行心脏彩超检测心脏功能、Masson染色检测瘢痕组织增生、免疫荧光法检测细胞凋亡和血管形成。结果与其他两组相比,Ang1-PLGA-PEG纳米微粒可以增加心肌梗死周围区域血管密度和成熟度(P＜0.05),抑制心肌细胞凋亡 (P＜0.05),显著减少心肌梗死面积 (P＜0.05),减少心肌病理性重塑,提高心脏功能(P＜0.05)。结论 Ang1-PLGA-PEG纳米粒心肌局部注射可使心肌梗死区域血管增生、心肌细胞凋亡及心肌梗死面积减少,从而提高了心肌梗死大鼠的心功能。为临床应用提供了实验依据。

关键词: 血管生成素1, PLGA-PEG纳米微粒, 心肌修复

Abstract: Objective To investigate the effect of PLGA-PEG scaffold incorporating angiopoietin 1(Ang1) loaded nanoparticle that was injected into the infarcted area of rat heart to protect the heart from infarction and explore potential mechanisms. Methods Rat models of myocardial infarction were replicated,and one week later SD rats were randomly divided into 3 groups:Ang1-PLGA-PEG injection group [injected with 100 μL nanoparticle suspension, about (1.61±0.05)μg Ang1](n=9),Ang1 injection group[injected with PBS solution of angiopoietin1(100 μL, 25 ng/μL)](n=8),the model control group(injected with 100 μL PBS solution)(n=8). Four weeks after injection,cardiac function was examined by echocardiography,scar tissue hyperplasia was measured by Masson staining, cardiomyocyte apoptosis and angiogenesis were detected by immunofluorescence. Results In comparison with other two groups,Ang1-PLGA-PEG injection group showed an increased blood vessel density in the infarcted area and maturity(P＜0.05),which prevented cardiomyocyte apoptosis (P＜0.05) The area of myocardial infarction was significantly decreased(P＜0.05), the remodeling of cardiomyopathy was reduced and these changes improved cardiac function (P＜0.05). Compared with the model control group, pure Ang1 injected into the surrounding area did not show curative effect (P＜0.05). Conclusions Injection of Ang1-PLGA-PEG nanoparticles into the infarcted area of left ventricle may promote vascular proliferation and facilitate the survival of cardiomyocytes,It provides an experimental basis for clinical application.

Key words: angiopoietin 1, PLGA-PEG nanoparticles, cardiac regeneration

中图分类号:

R605

方涛, 杨婉浠, 李昕, 丛志成, 张沛宗, 祁泉, 宋兵. 负载血管生成素1的聚乳酸羟基乙酸-聚乙二醇纳米微粒促进大鼠心肌梗死后心肌修复[J]. 基础医学与临床, 2021, 41(8): 1114-1120.

FANG Tao, YANG Wan-xi, LI Xin, CONG Zhi-cheng, ZHANG Pei-zong, QI Quan, SONG Bing. Poly (lactic-co-glycolic acid)-poly (ethylene glycol) scaffold incorporating angiopoietin 1 loaded nanoparticles promotes cardiac repair after myocardial infarction in rats[J]. Basic & Clinical Medicine, 2021, 41(8): 1114-1120.

参考文献

[1]Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: a report from the american heart association[J]. Circulation, 2018, 137: 67-492.
[2]Tzahor E, Poss KD. Cardiac regeneration strategies: staying young at heart[J]. Science, 2017, 356: 1035-1039.
[3]Rubanyi GM. Mechanistic, technical, and clinical perspectives in therapeutic stimulation of coronary collateral development by angiogenic growth factors[J]. Mol Ther, 2013, 21: 725-738.
[4]Pascual-Gil S, Simón-Yarza T, Garbayo E, et al. Cytokine-loaded plga and peg-plga microparticles showed similar heart regeneration in a rat myocardial infarction model[J]. Int J Pharm, 2017, 523: 531-533.
[5]Bhargava-Shah A, Foygel K, Devulapally R, et al. Orlistat and antisense-mirna-loaded plga-peg nanoparticles for enhanced triple negative breast cancer therapy[J]. Nanomedicine (Lond), 2016, 11: 235-247.
[6]Reis LA, Chiu LL, Wu J, et al. Hydrogels with integrin-binding angiopoietin-1-derived peptide, qhredgs, for treatment of acute myocardial infarction[J]. Circ Heart Fail, 2015, 8: 333-341.
[7]Hasegawa T, Kimura A, Miyataka M, et al. Basic fibroblast growth factor increases regional myocardial blood flow and salvages myocardium in the infarct border zone in a rabbit model of acute myocardial infarction[J]. Angiology, 1999, 50: 487-495.
[8]Ruvinov E, Leor J, Cohen S. The promotion of myocardial repair by the sequential delivery of igf-1 and hgf from an injectable alginate biomaterial in a model of acute myocardial infarction[J]. Biomaterials, 2011, 32: 565-578.
[9]Song M, Jang H, Lee J, et al. Regeneration of chronic myocardial infarction by injectable hydrogels containing stem cell homing factor sdf-1 and angiogenic peptide ac-sdkp[J]. Biomaterials, 2014, 35: 2436-2445.
[10]Kim JH, Jung Y, Kim SH, et al. The enhancement of mature vessel formation and cardiac function in infarcted hearts using dual growth factor delivery with self-assembl-ing peptides[J]. Biomaterials, 2011, 32: 6080-6088.
[11]Badimon L, Borrell M. Microvasculature recovery by angiogenesis after myocardial infarction[J]. Curr Pharm Des, 2018, 24: 2967-2973.
[12]王梓豪, 贺继刚, 谢巧丽,等. 过表达gata-4的小鼠骨髓间充质干细胞改善小鼠心肌梗死后的心功能[J]. 基础医学与临床, 2019, 39: 1229-1233.
[13]Potz BA, Parulkar AB, Abid RM, et al. Novel molecular targets for coronary angiogenesis and ischemic heart disease[J]. Coron Artery Dis, 2017, 28: 605-613.