创伤较小的小鼠主动脉弓缩窄术的建立
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国家自然科学基金(81102829);教育部新世纪优秀人才支持计划(NCET-13-0692)。


Establishment of a mouse model of transverse aortic constriction with less invasive injury
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    摘要:

    目的 探索一种对小鼠创伤较小的主动脉弓缩窄术的手术方法。方法 32只雄性昆明(KM)小鼠,随机分为假手术10只及模型(主动脉弓缩窄术)组22只;模型组动物麻醉后仰卧位固定,行气管插管接通呼吸机。右侧卧位重新固定,左侧第二肋间开胸,分离主动脉弓并用5-0真丝编织线将其套扎在26G注射器针头行缩窄操作,缩窄后退出针头,关胸。假手术组动物同期行开胸,而不进行缩窄操作,其余操作步骤与模型组相同。造模期间及造模后4周记录动物死亡情况;于术后4周对两组小鼠行心脏超声及心脏病理学检测。结果 ①模型组总死亡率约为32%。②超声心动图结果:模型组主动脉弓缩窄处血流速率均大于2 400 mm/s;假手术组主动脉弓缩窄处血流速率均小于900 mm/s。与假手术组比较,模型组左室收缩末期内径(LVSD)、左心室收缩期容积(LVSV)、左心室重量(LV mass, LVM)、左心室重量指数(LV mass index, LVMI)明显增加(P<0.05);射血分数(EF)、左心室缩短分数(FS)显著降低(P<0.05)。③病理切片可见血管扩张及血管壁增厚表现。结论 本造模方法能够成功增加心脏后负荷,诱导后负荷增加所致的心肌肥厚病理生理过程。与国内报道较多的劈开胸骨的造模方法相比,该造模方法对模型动物的损伤更小,在与心肌肥厚病理生理机制及相关药效研究中具有很大的应用价值。

    Abstract:

    Objective To explore a method of establishment of a mouse model of transverse aortic constriction(TAC) with less invasive injury. Methods Thirty-two male KM mice were randomly divided into two groups: sham-operation(SH) group (n=10)and transverse aortic constriction(TAC)group(n=22).Mice of the TAC group were placed in a supine position under anesthesia. The endotracheal intubation tube was then connected on a rodent ventilator.After that,the mice were replaced in the right lateral decubitus position. Thoracotomy was performed to the second rib and to separate the transverse aorta. A 26G blunt needle was inserted into thetransverse aorta, and a small piece of 5-0 silk thread was used to tightly ligate the needle inserted in the transverse aorta. The same operation was performed on the mice of sham group, except for the ligation of the transverse aorta. Then the open chest was closed and the skin was sutured. The death of mice during and post operation was recorded. Echocardiographic assessments,heart weight and histological examination of the myocardium were performed at 4 weeks after surgery.Results ① The total death rate of TAC modeling was 32%. ②The blood flow velocities of the ligation of transverse aorta were all above 2400 mm/s in the TAC group,but all bellow 900 mm/s in the SH group. Compared with that in the sham operation group, the LVSD, LVDV,LVM, and LVMI were significantly increased (P<0.05), and the EF and FS were significantly decreased in the TAC group (P<0.05).③Histopathological examination showed vascular dilation and thickening of the blood vessel wall. Conclusions The method of establishing a mouse model of transverse aortic constriction can successfully induce pressure overload, resulting in myocardial hypertrophy and heart failure. Compared with the widely reported literature in our country, this method does not need to split the sternum and causes less invasive injury. Therefore, it may have good application value in myocardial hypertrophy-related pathophysiological and pharmacodynamics studies.

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廉洪建,冯玄超,啜文静,薛晓兴,王伟,郭淑贞.创伤较小的小鼠主动脉弓缩窄术的建立[J].中国比较医学杂志,2015,25(2):42~45.

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  • 最后修改日期:2014-11-15
  • 在线发布日期: 2015-03-04
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