CN110664794A - 氨基氧乙酸在制备预防或治疗心梗的药物中的应用 - Google Patents
氨基氧乙酸在制备预防或治疗心梗的药物中的应用 Download PDFInfo
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Abstract
本发明公开了氨基氧乙酸在制备预防或治疗心梗的药物或保健品中的应用;氨基氧乙酸改善心梗后心功能,减小心梗面积,从而可以预防或者治疗心梗。
Description
技术领域
本发明属于药物技术,具体涉及氨基氧乙酸在制备预防或治疗急性心梗的药物中的应用。
背景技术
心肌梗死是一种严重危害人类健康的心血管疾病,随着我国人民生活水平的不断提高,缺血性心肌梗死的发病率也在不断上升。缺血性心肌梗死会导致瘢痕形成,进而影响心脏功能。目前药物或器械治疗大多只能缓解症状,但却不能逆转心脏组织损伤。心脏移植虽能彻底改善心脏状态,但因供体来源稀缺、免疫排斥以及昂贵的治疗费用等因素,在临床上很难广泛应用。目前有研究报道氨基氧乙酸(Aminooxyacetic acid,AOAA)在制备治疗肝细胞肝癌的药物中的应用,但迄今为止尚未见氨基氧乙酸治疗心肌梗死方面的研究报道。
发明内容
为解决上述现有技术存在的问题,本发明的目的在于提供一种利用AOAA改善心梗后心功能的新用途。
本发明公开了氨基氧乙酸在制备预防或治疗心梗的药物或保健品中的应用。
本发明中,所述药物为注射制剂。
本发明涉及的AOAA在制备预防或治疗心梗药物或保健品中的应用,具体的是AOAA可用于制备心梗保护或者治疗的药物,具体的给药方式可采取腹腔注射等。
本发明选用25g左右的C57BL/6J雄性小鼠为实验对象,采用左冠状动脉前降支结扎法制作心梗模型,实验符合统计要求。腹腔注射麻醉后,经口气管插管,接空气呼吸机,呼吸频率110次/min,潮气量3ml,吸呼比1:1.3。右侧卧位,左胸纵切口切开外层皮肤,剥离胸大肌,第三、四肋间横切口开胸,暴露心脏,用镊子撕开心包膜。借助手术显微镜可见左冠状动脉大致走行。在左心耳下缘约1.5mm处,将冠状动脉前降支(LAD) 连同少量心肌组织一起结扎,进针深度约1 mm,宽度控制在3 mm以内。逐层关胸。结扎后肉眼可见结扎处至心尖变白,证明心梗模型建立成功。实验组小鼠心梗术后连续3天行腹腔注射AOAA(10 mg/kg/天),然后常规喂养。将心脏超声诊断仪探头置于心前壁,于乳头肌水平取左室二维短轴观,同时记录M型扫描,连续3个心动周期测量左室射血分数(EF)、缩短分数(FS)和左室舒张末径(LVEDD)和左室收缩末径(LVESD),心梗术后28天检测心功能,AOAA显著改善心梗后心功能、射血分数和短轴缩短率;术后28天处死小鼠,取左心室组织进行心脏组织染色,观察治疗效果。按常规Masson染色步骤进行,在普通光学显微镜下观察并拍照。采用图像分析软件Image J分析各部分面积,计算心梗面积/心脏面积;以Masson染色观察各组心梗术后28天梗死面积,发现AOAA有效减小心梗面积。
本发明公开了氨基氧乙酸改善心梗后心功能,减小心梗面积,从而可以预防或者治疗心梗。
附图说明
图1为心肌梗死造模前后各组心脏M型超声示意图;
图2为心肌梗死后28天,射血分数(EF)动态变化曲线;
图3为心肌梗死后28天,短轴缩短率(FS)动态变化曲线;
图4为心肌梗死后28天,Masson染色分析各组心梗面;
图5为心肌梗死后28天,各组心梗面积统计。
具体实施方式
所使用的主要材料和来源分别如下:
C57BL/6J小鼠(昭衍(苏州)新药研究中心提供,此实验由苏州大学伦理委员会批准);小动物呼吸机(上海奥尔科特生物科技有限公司,上海);手术器械(六六视觉公司,苏州);缝合针线(上海浦东金环医疗用品有限公司,上海);小动物超声影像系统(Visual SonicsVevo 2100);氨基氧乙酸(Aminooxyacetic acid,AOAA)购自sigma。
小鼠心肌梗死模型的建立
选用25g左右的C57BL/6J雄性小鼠为实验对象,采用左冠状动脉前降支结扎法制作心梗模型,实验符合统计要求。腹腔注射麻醉后,经口气管插管,接空气呼吸机,呼吸频率110次/min,潮气量3ml,吸呼比1:1.3。右侧卧位,左胸纵切口切开外层皮肤,剥离胸大肌,第三、四肋间横切口开胸,暴露心脏,用镊子撕开心包膜。借助手术显微镜可见左冠状动脉大致走行。在左心耳下缘约1.5mm处,将冠状动脉前降支(LAD) 连同少量心肌组织一起结扎,进针深度约1 mm,宽度控制在3 mm以内。逐层关胸。结扎后肉眼可见结扎处至心尖变白,证明心梗模型建立成功。实验组小鼠心梗术后连续3天进行腹腔注射AOAA(10 mg/kg/天),对照组小鼠注射等量无菌生理盐水作为对照。喂养方式一致,然后进行心梗后心功能、心梗面积检测。
实施例1:AOAA有效改善心梗后心功能
心脏超声检测心梗后心功能
小鼠麻醉(方法同前),脱毛后左侧卧位,将心脏超声诊断仪探头置于心前壁,于乳头肌水平取左室二维短轴观,同时记录M型扫描,连续3个心动周期测量左室射血分数(EF)、缩短分数(FS)和左室舒张末径(LVEDD)和左室收缩末径(LVESD)。
实验结果:心梗术后28天检测心功能,AOAA显著改善心梗后心功能(图1),射血分数(图2)和短轴缩短率(图3)均有显著改善;*P < 0.05。
实施例2:AOAA有效减小心梗面积
Masson染色:术后28天处死小鼠,取左心室组织进行心脏组织染色,观察治疗效果。按常规Masson染色步骤进行,在普通光学显微镜下观察并拍照。采用图像分析软件Image J分析各部分面积,计算心梗面积/心脏面积;
实验结果:以Masson染色观察各组心梗术后28天梗死面积(图4 & 5),发现AOAA有效减小心梗面积;*P < 0.05。
【结论】
上述结果综合证明:AOAA能有效改善心梗后心功能,有效减小心梗面积,从而可以预防或者治疗心梗。
以上所述仅是本发明的优选实施方式,应当指出:对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以做出若干改进和润饰,这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.氨基氧乙酸在制备预防或者治疗心梗的药物中的应用。
2.根据权利要求1所述的应用,其特征在于,所述药物为注射制剂。
3.根据权利要求1所述的应用,其特征在于,氨基氧乙酸改善心梗后心功能。
4.根据权利要求1所述的应用,其特征在于,氨基氧乙酸减小心梗面积。
5.氨基氧乙酸在制备改善心梗后心功能的药物中的应用。
6.根据权利要求5所述的应用,其特征在于,所述药物为注射制剂。
7.氨基氧乙酸在制备减小心梗面积的药物中的应用。
8.根据权利要求7所述的应用,其特征在于,所述药物为注射制剂。
9.氨基氧乙酸在制备预防心梗的保健品中的应用。
10.根据权利要求9所述的应用,其特征在于,所述保健品为注射品。
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