小脑延髓池弹性蛋白酶注射制作小鼠椎基底动脉延长扩张症模型和磁共振血管造影评价

Elastase injection into the cerebellomedullary cistern to induce a model of vertebrobasilar dolichoectasia in mice and evaluation of magnetic resonance angiography

目的探讨磁共振血管造影(magnetic resonance angiography,MRA)评价小脑延髓池注射弹性蛋白酶诱导小鼠椎基底动脉延长扩张症(vertebrobasilar dolichoectasia,VBD)动物模型的效果。方法选取雄性SPF级C57/BL6小鼠24只,弹性蛋白酶组小鼠(n=12)小脑延髓池注射2.5μl含有25 mU弹性蛋白酶的磷酸盐缓冲液,生理盐水对照组小鼠(n=12)注射等体积生理盐水。模型制作后2周进行活体小鼠头颅MRA检查。模型制作成功定义为基底动脉弯曲成角≤170°,或基底动脉弯曲长度占比≥10%,或基底动脉偏离中线1级以上,或动脉直径增加百分比≥25%。结果弹性蛋白酶组和生理盐水对照组分别有2只和1只小鼠未正常苏醒或死亡。生理盐水对照组11只存活小鼠均未见明显椎动脉和基底动脉异常,弹性蛋白酶组10只存活小鼠造模成功率为80%,两组之间成功率差异有统计学意义(P<0.05)。弹性蛋白酶组与生理盐水对照组存活小鼠平均基底动脉直径(0.30 mm对0.22 mm;P<0.05)、平均基底动脉弯曲成角(115°对170°;P<0.05)以及平均基底动脉弯曲长度占比(31%对5%;P<0.05)均差异有统计学意义。结论MRA能较好地评价小脑延髓池注射弹性蛋白酶诱导的小鼠VBD模型。

Objective To investigate the effect of magnetic resonance angiography(MRA)in evaluating the mouse model of vertebrobasilar dolichoectasia(VBD)induced by injection of elastase into cerebellomedullary cistern.Methods Twenty-four male C57/BL6 mice were selected.The mice in the elastase group(n=12)were injected in the cerebellomedullary cistern with 2.5μl of phosphate buffer containing 25 mU elastase,and the mice in the saline control group(n=12)were injected with the same volume of normal saline.MRA examination of the brains of living mice was performed 2 weeks after modeling.Successful modeling was defined as the basilar artery bending angle≤170°,or the basilar artery bending length accounts for≥10%,or the basilar artery deviated from the midline by more than 1 grade,or the percentage increase in artery diameter was≥25%.Results In the elastase group and the saline control group,2 mice and 1 mouse did not wake up normally or died,respectively.The 11 surviving mice in the saline control group had no obvious vertebral artery and basilar artery abnormalities.The success rate of modeling in the 10 surviving mice in the elastase group was 80%,and the difference in the success rate between the two groups was statistically significant(P<0.05).There were significant differences in mean basilar artery diameter(0.30 mm vs.0.22 mm;P<0.05),mean basilar artery bending angle(115°vs.170°;P<0.05),and proportion of mean basilar artery bending length(31%vs.5%;P<0.05)of the surviving mice between the elastase group and the saline control group.Conclusion MRA can better evaluate the mouse VBD model induced by elastase injection in the cerebellomedullary cistern.