负载尼洛替尼的甲基丙烯酰化明胶微针贴片治疗心肌梗死后心脏功能障碍的研发与应用

Nilotinib-loaded gelatin methacryloyl microneedles patch for the treatment of cardia dysfunction after myocardial infarction

本研究旨在评价负载尼洛替尼的生物相容性甲基丙烯酰化明胶(GelMA)微针贴片应用于心肌梗死(简称:心梗)后对心脏功能障碍的治疗作用,为临床抗心肌纤维化治疗提供新的思路。本研究在心梗造模后10 d(疤痕成熟期),将GelMA微针贴片贴附于心外膜表面,靶向梗死及周围区递送抗纤维化药物尼洛替尼。在心梗造模后28 d,通过超声心动图、血浆脑型利钠肽、心重/体重比等指标评价心脏功能和左室重构情况;通过小麦胚芽凝集素染色评价心肌肥大情况;通过苏木精—伊红染色、天狼星红染色评价心肌纤维化情况。结果显示,相较于心梗对照组及使用空白GelMA微针贴片治疗组,负载尼洛替尼的GelMA微针贴片可减轻心肌肥大和梗死周围区纤维化过度扩张,从而预防不良心室重构,改善心功能。本研究所提这一治疗策略是纠正心梗后心脏功能障碍的一次有益尝试,有望成为纠正心梗后心脏功能障碍的新策略,对改善心梗患者的长期预后具有重要的临床意义。

The study aimed to evaluate the therapeutic effect of nilotinib-loaded biocompatible gelatin methacryloyl(GelMA)microneedles patch on cardiac dysfunction after myocardial infarction(MI),and provide a new clinical perspective of myocardial fibrosis therapies.The GelMA microneedles patches were attached to the epicardial surface of the infarct and peri-infarct zone in order to deliver the anti-fibrosis drug nilotinib on the 1oth day after MI,when the scar had matured.Cardiac function and left ventricular remodeling were assessed by such as echocardiography,BNP(brain natriuretic peptide)and the heart weight/body weight ratio(HW/BW).Myocardial hypertrophy and fibrosis were examined by WGA(wheat germ agglutinin)staining,HE(hematoxylin-eosin staining)staining and Sirius Red staining.The results showed that the nilotinib-loaded microneedles patch could effectively attenuate fibrosis expansion in the peri-infarct zone and myocardial hypertrophy,prevent adverse ventricular remodeling and finally improve cardiac function.This treatment strategy is a beneficial attempt to correct the cardiac dysfunction after myocardial infarction,which is expected to become a new strategy to correct the cardiac dysfunction after MI.This is of great clinical significance for improving the long-term prognosis of MI patients.