CN110692599A - 一种胸腹主动脉瘤小鼠模型的制备方法 - Google Patents
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Abstract
本发明提供了一种胸腹主动脉瘤小鼠模型的制备方法，先选择9‑11周龄的C57BL/6小鼠，将β‑氨基丙腈(beta‑aminopropionitrile，BAPN)以150mg/kg/day的量通过动物微量给药渗透压泵在皮下持续泵入，一共持续2周；同时将血管紧张素II以1000ng/kg/min的量通过动物微量给药渗透压泵在皮下持续泵入，一共持续6周，获得胸腹主动脉瘤小鼠模型。本发明采用β‑氨基丙腈联合血管紧张素II的方法诱导C57BL/6小鼠的胸腹主动脉瘤形成，建立的模型更加符合主动脉瘤形成的病理生理机制，有利于进一步探讨主动脉瘤的病变机制。
Description
技术领域
本发明属于生物学领域，涉及一种动物模型，具体来说是一种胸腹主动脉瘤小鼠模型的制备方法。
背景技术
随着对主动脉瘤的病理生理机制的进一步研究，其炎症和平滑肌细胞凋亡引起弹力膜的稳定性下降，血管壁弹力和张力下降而导致管壁的扩张和动脉瘤形成。
目前主要有三种建立动脉瘤模型的方法，小鼠血管紧张素Ⅱ诱导法(主要是选用ApoE-/-小鼠+高脂饮食)，其动脉瘤形成的比例较低，且动脉瘤常在粥样斑块形成后才逐渐出现，周期较长，且成瘤部位几乎均为腹主动脉。弹性蛋白酶灌注法(操作复杂，且操作难度大，也很少应用于小型动物的主动脉瘤的建模中)，和CaCl2血管周围浸润法(通过手术使某一部位的动脉局限性扩张)。
目前的方法与主动脉瘤形成的机制过程并不完全相符，并不能很好的探讨主动脉瘤发生发展的过程。
发明内容
针对现有技术中的上述技术问题，本发明提供了一种胸腹主动脉瘤小鼠模型的制备方法，所述的这种胸腹主动脉瘤小鼠模型的制备方法要解决现有技术中的胸腹主动脉瘤小鼠模型的制备方法与主动脉瘤形成的机制过程并不完全相符，并不能很好的探讨主动脉瘤发生发展的过程。
本发明提供了一种胸腹主动脉瘤小鼠模型的制备方法，包括如下步骤：
1)选择9-11周龄的C57BL/6小鼠，将β-氨基丙腈以150mg/kg/day的量通过动物微量给药渗透压泵在皮下持续泵入，一共持续2周；
2)同时将血管紧张素II以1000ng/kg/min的量通过动物微量给药渗透压泵在皮下持续泵入，一共持续6周，获得胸腹主动脉瘤小鼠模型。
进一步，所述动物微量给药渗透压泵给药是从小鼠背部皮下植入。
为了寻找一种更加符合动脉瘤发生发展的成瘤方式，以便更好对其机制进行研究。本发明采用BAPN联合血管紧张素II的方法诱导C57BL/6小鼠的胸腹主动脉瘤形成，建立的模型更加符合主动脉瘤形成的病理生理机制，有利于进一步探讨主动脉瘤的病变机制。
本发明所采用的β-氨基丙腈是一种赖氨酸氧化酶抑制剂，通过破坏弹性膜的稳态，导致弹性膜的降解。本发明建立的模型更加符合主动脉瘤形成的病理生理机制，有利于进一步探讨动脉瘤的形成过程。
本发明和已有技术相比，其技术进步是显著的。本发明建立了一种BAPN联合血管紧张素II C57BL/6小鼠主动脉瘤模型，通过本发明的方法获得的模型更加符合主动脉瘤发生发展的病理生理过程，并且能够成功诱导多部位成瘤，如升主动脉瘤、胸主动脉瘤和腹主动脉瘤的形成，操作相对简单，成瘤率高(约70％)，同时形态学、组织病理学更符合主动脉瘤的演变过程。
附图说明
图1显示了本发明一种胸腹主动脉瘤小鼠模型的制备方法的流程图。
图2显示了采用本发明的方法制备的模型和正常小鼠的比较情况。
图3显示了本发明方法制备的模型小鼠的成瘤率和动脉直径与正常小鼠的比较。
具体实施方式
实施例1
如图1所示，本发明提供了一种胸腹主动脉瘤小鼠模型的制备方法，包括如下步骤：
1)选择9-11周龄的C57BL/6小鼠，将β-氨基丙腈beta-aminopropionitrile(BAPN)(Energy Chemical,Shanghai,China)以150mg/kg/day的量通过动物微量给药渗透压泵osmotic pump(Alzet,Cupertino,CA,USA)皮下持续泵入，一共持续2周；
2)同时将血管紧张素II(ApexBio,Boston,MA,USA)以1000ng/kg/min的量通过动物微量给药渗透压泵osmotic pump(Alzet,Cupertino,CA,USA)皮下持续泵入，一共持续6周，获得胸腹主动脉瘤小鼠模型。
具体的，所述动物微量给药渗透压泵是从小鼠背部皮下植入。
如图2所示，对泵入药物6周后的小鼠予以断颈处死，解剖其完整的全长主动脉，通过与同期对照的正常小鼠全长主动脉进行比较，发现其主动脉直径要大于正常小鼠，呈瘤样改变；其中，图2A是正常C57BL/6小鼠的大体血管，图2B是动脉瘤模型C57BL/6小鼠的大体血管。动脉瘤模型的小鼠其动脉直径要大于正常小鼠。
通过将本发明方法制备的模型小鼠的成瘤率和动脉直径与正常小鼠的比较，如图3所示，A为主动脉成瘤率(％)，显示模型小鼠的成瘤率约为70％，而正常小鼠无动脉瘤形成。
B为主动脉直径(mm)；显示模型小鼠的主动脉直径为1.8±0.2mm，而正常小鼠主动脉直径为1.0±0.1mm，有明显的统计学差异(P<0.01)。
有上述实验可知，采用本发明的方法获得的模型更加符合动脉瘤发生发展的病理生理过程，并且能够成功诱导升主动脉瘤、胸主动脉瘤和腹主动脉瘤，且无需开胸手术，成瘤率高(约70％)，同时形态学、组织病理学符合主动脉瘤模型。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等，均应包含在本发明的保护范围之内。
Claims (2)
1.一种胸腹主动脉瘤小鼠模型的制备方法，其特征在于包括如下步骤：
1)选择9-11周龄的C57BL/6小鼠，将β-氨基丙腈以150mg/kg/day的量通过动物微量给药渗透压泵在皮下持续泵入，一共持续2周；
2)同时将血管紧张素II以1000ng/kg/min的量通过动物微量给药渗透压泵在皮下持续泵入，一共持续6周，获得胸腹主动脉瘤小鼠模型。
2.根据权利要求1所述的一种胸腹主动脉瘤小鼠模型的制备方法，其特征在于：所述动物微量给药渗透压泵给药是从小鼠背部皮下植入。
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| CN114667967A (zh) * | 2022-03-02 | 2022-06-28 | 大连医科大学附属第二医院 | 一种持续血管紧张素ii灌注引起的小鼠高血压眼底病变模型的制备方法及其应用 |
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