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在犬慢性心肌梗死模型中使用可生物降解明胶水凝胶片持续释放碱性成纤维细胞生长因子的治疗性血管生成。

A therapeutic angiogenesis of sustained release of basic fibroblast growth factor using biodegradable gelatin hydrogel sheets in a canine chronic myocardial infarction model.

作者信息

Kumagai Motoyuki, Minakata Kenji, Masumoto Hidetoshi, Yamamoto Masaya, Yonezawa Atsushi, Ikeda Takafumi, Uehara Kyokun, Yamazaki Kazuhiro, Ikeda Tadashi, Matsubara Kazuo, Yokode Masayuki, Shimizu Akira, Tabata Yasuhiko, Sakata Ryuzo, Minatoya Kenji

机构信息

Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

Department of Cardiovascular Surgery, Hamamatsu Rosai Hospital, Hamamatsu, Japan.

出版信息

Heart Vessels. 2018 Oct;33(10):1251-1257. doi: 10.1007/s00380-018-1185-6. Epub 2018 May 14.

Abstract

This study investigated the safety and efficacy of a sustained release of basic fibroblast growth factor (bFGF) with biodegradable gelatin hydrogel sheets as therapeutic angiogenesis in canine chronic myocardial infarction (MI) models. Canine chronic MI model was induced by ligating the left anterior descending coronary artery and its diagonal branches. At 4 week post-induction, we applied either saline (Control group, n = 5) or 200 μg of bFGF (Treatment group, n = 6) soaked gelatin hydrogel sheets on the ischemic area of the left ventricular (LV) wall. At 6 weeks after the procedure, we evaluated the efficacy by echocardiography and immunohistochemical study. There were no procedure-related adverse events or deaths. The serum bFGF level was under detectable levels in all animals at any sampling points. In terms of efficacy, echocardiographic evaluation demonstrated that fractional shortening was significantly improved in the treatment group. In addition, immunohistochemical study showed that the capillary density in the border zone of the MI area, as well as the MI area, significantly increased in the treatment group. Therapeutic angiogenesis by bFGF using biodegradable gelatin hydrogel sheets was safe, increased the capillary density, and improved LV function in canine chronic MI models.

摘要

本研究调查了以可生物降解的明胶水凝胶片持续释放碱性成纤维细胞生长因子(bFGF)用于犬慢性心肌梗死(MI)模型中治疗性血管生成的安全性和有效性。通过结扎左冠状动脉前降支及其对角支诱导犬慢性MI模型。诱导后4周,我们将浸泡过生理盐水的明胶水凝胶片(对照组,n = 5)或200μg bFGF(治疗组,n = 6)应用于左心室(LV)壁的缺血区域。术后6周,我们通过超声心动图和免疫组织化学研究评估疗效。未发生与手术相关的不良事件或死亡。在任何采样点,所有动物的血清bFGF水平均低于可检测水平。在疗效方面,超声心动图评估显示治疗组的缩短分数显著改善。此外,免疫组织化学研究表明,治疗组MI区域边缘区以及MI区域的毛细血管密度显著增加。在犬慢性MI模型中,使用可生物降解明胶水凝胶片通过bFGF进行治疗性血管生成是安全的,可增加毛细血管密度并改善LV功能。

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