负载肝细胞生长因子水凝胶对心肌梗死组织区域的作用  

Effects of hydrogels loaded with hepatocyte growth factor on myocardial infarction

作　　者：王南峰 沈胜梅 张佩生[1] 滕伟[3] Wang Nanfeng;Shen Shengmei;Zhang Peisheng;Teng Wei(The Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450015,Henan Province,China;Nanshi Hospital of Nanyang,Nanyang 473000,Henan Province,China;The First Affiliated Hospital of Henan University,Kaifeng 410200,Henan Province,China)

机构地区：[1]郑州大学第五附属医院,河南省郑州市450015 [2]河南大学附属南石医院,河南省南阳市473000 [3]河南大学第一附属医院,河南省开封市410200

出　　处：《中国组织工程研究》2023年第30期4802-4808,共7页Chinese Journal of Tissue Engineering Research

基　　金：河南省医学科技攻关计划(LHGJ20190506),项目负责人:滕伟。

摘　　要：背景:研究证实肝细胞生长因子可显著减轻糖尿病大鼠心肌梗死后心肌细胞凋亡、改善心功能,但是以往的研究多是静脉注射或是基因转染的给药方式,利用药物缓释系统给药的研究不多见。目的:以水凝胶作为肝细胞生长因子的载体,有效注射至心肌梗死部位,观察其改善心功能的效果。方法:制备甘油磷酸钠/壳聚糖/海藻酸钠/肝细胞生长因子水凝胶,检测该水凝胶对心肌细胞的相容性与体外生长因子释放特征。取3月龄雄性SD大鼠54只,结扎冠状动脉左前降分支复制心肌梗死模型,采用随机数字表法分3组处理:未治疗组于心肌梗死边缘分多点注射PBS,无生长因子水凝胶组于心肌梗死边缘分多点注射甘油磷酸钠/壳聚糖/海藻酸钠水凝胶,载生长因子水凝胶组心肌梗死边缘分多点注射甘油磷酸钠/壳聚糖/海藻酸钠/肝细胞生长因子水凝胶,每组18只,于设定时间点进行相关检测。结果与结论:①活死染色与CCK-8实验结果显示,甘油磷酸钠/壳聚糖/海藻酸钠/肝细胞生长因子水凝胶具有良好的细胞相容性,可促进心肌细胞的增殖与存活;甘油磷酸钠/壳聚糖/海藻酸钠/肝细胞生长因子水凝胶可持续释放肝细胞生长因子达42 d以上;②造模后第7,14,35天,与未治疗组、无生长因子水凝胶组比较,载生长因子水凝胶组大鼠舒张末期左室容积及收缩末期左室容积减小(P<0.05),左室射血分数、左室短轴缩短率增加(P<0.05);③造模后第35天的苏木精-伊红与Masson染色显示,与未治疗组相比,两治疗组大鼠心肌组织病理均有明显改善,其中以载生长因子水凝胶组改善更明显;④造模后第35天的Tunel染色与α-平滑肌肌动蛋白免疫荧光染色显示,载生长因子水凝胶组大鼠的心肌细胞凋亡数量低于未治疗组、无生长因子水凝胶组(P<0.05),微血管密度大于未治疗组、无生长因子水凝胶组(P<0.05);⑤结果表明,将甘油�BACKGROUND:Hepatocyte growth factor(HGF)has been shown to reduce cardiomyocyte apoptosis and improve cardiac function after myocardial infarction in diabetic rats.Intravenous injection or gene transfection is common methods of drug delivery in many previous studies;however,a sustained release system was used in very few studies.OBJECTIVE:To investigate the effects of intramyocardial injection of hydrogels loaded with HGF on myocardial infarction.METHODS:The sodium glycerophosphate/chitosan/sodium alginate/HGF composite hydrogel was prepared,and the compatibility of the hydrogel with cardiomyocytes and the release characteristics of growth factors in vitro were detected.A total of 54 male Sprage-Dawley rats(3 months old)were used for the establishment of myocardial infarction models by ligating the left anterior descending branch of the coronary artery and equally and randomly divided into three groups:untreated(multi-point injection of PBS at the edge of myocardial infarction),hydrogel without HGF(multi-point injection of sodium glycerophosphate/chitosan/sodium alginate composite hydrogel at the edge of myocardial infarction),and hydrogel with HGF(multi-point injection of sodium glycerophosphate/chitosan/sodium alginate/HGF composite hydrogel at the edge of myocardial infarction)groups.RESULTS AND CONCLUSION:(1)Live-dead cell staining and CCK-8 assay showed that sodium glycerophosphate/chitosan/sodium alginate/hepatocyte growth factor hydrogel had good cytocompatibility and promoted the proliferation and survival of cardiomyocytes and could sustainably release HGF for more than 42 days.(2)The left ventricular volume and left ventricular volume at the end of diastole were significantly decreased in the hydrogel with HGF groups(P<0.05),while the left ventricular ejection fraction and left ventricular short-axis shortening rate were significantly increased(P<0.05)compared with the other two groups at 7,14,35 days after surgery.(3)Hemotoxylin-eosin and Masson stainings showed that the myocardial histopathology of rat

关 键 词：心肌梗死 水凝胶 肝细胞生长因子 心功能 心血管疾病 药物缓释 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R541