弹性蛋白酶注射部位及结扎动脉对小鼠颅内动脉瘤模型成瘤率的影响  

Comparative Study on the Infection Efficiency of Different Adeno-associated Virus on Circulus Arteriosus Cerebri in Mice

作　　者：李昊 徐昊辰 温红艳 平杰丹 陶瑾 刘晶 陈敬洲[1] LI Hao;XU Hao-chen;WEN Hong-yan;PING Jie-dan;TAOJin;LIU Jing;CHEN Jing-zhour(State Key Laboratory of Cardiovascular Disease,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100037,China;Department of Ultrasound,Fuwai Hospital,National Center for Cardiovascular Diseases,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100037,China)

机构地区：[1]北京协和医学院中国医学科学院,国家心血管病中心阜外医院心血管疾病国家重点实验室,北京市100037 [2]北京协和医学院中国医学科学院,国家心血管病中心阜外医院超声影像中心,北京市100037

出　　处：《中国分子心脏病学杂志》2021年第2期3877-3882,共6页Molecular Cardiology of China

基　　金：中国医学科学院医学与健康科技创新工程项目(2016-I2M-1-015)。

摘　　要：目的探索弹性蛋白酶注射的两种不同部位以及结扎左颈总动脉及右肾动脉对于小鼠颅内动脉瘤成瘤率及破裂率的影响。方法16周龄C57BL/6雄性野生型小鼠行左颈总动脉及右肾动脉结扎,1周后依据脑定位图谱向囟前注射点定位坐标(前囟点前侧1.2mm,右侧0.7 mm,深5 mm)或囟后注射点定位坐标(前囟点后侧2.5 mm,右侧1.0mm,深5 mm)注射35 mU弹性蛋白酶,随即皮下植入血管紧张素Ⅱ微渗透泵。通过体视镜观察小鼠颅内动脉瘤成瘤及破裂,通过H&E染色观察脑血管形态,TUNEL染色评价血管平滑肌细胞凋亡。结果动脉结扎显著增加颅内动脉瘤模型小鼠成瘤率及破裂率,且该动脉结扎手术显著加重了Willis环血管平滑肌细胞凋亡水平。但无论选择前囟门前方位置还是后方位置进行弹性蛋白酶注射,对于颅内动脉瘤模型小鼠成瘤率及破裂率均无显著影响。结论给予动脉结扎手术能显著提高颅内动脉瘤动物模型成瘤率及破裂率,为研究颅内动脉瘤分子机制及药物干预方法提供了新的可靠动物模型。Objective To explore the effect of two different elastase injection sites,and ligation of left common carotid artery and right renal artery on the formation and rupture of intracranial aneurysms in mouse models.Methods 16-week-old C57 BL/6 mice underwent ligation of the left common carotid artery and right renal artery.One week later,according to the Mouse Brain Atlas,35 mU elastase was injected into the coordinates of the anterior fontanelle injection site(1.2 mm anterior to,0.7 mm on the right side of,and 5 mm below the anterior fontanelle point)and the coordinates of the posterior fontanelle injection site(2.5 mm posterior to,1.0 mm on the right side of,and 5 mm below the anterior fontanelle point).Subcutaneous infusion of angiotensin II was subsequently performed via implanted osmotic pumps.The formation and rupture of intracranial aneurysms in mice was observed by using stereoscope,the morphology of cerebral blood vessels was assessed by H&E staining,and the apoptosis of vascular smooth muscle cells was evaluated by TUNEL staining.Results Arterial ligation significantly increased the formation and rupture rate of intracranial aneurysms in mouse model,and arterial ligation surgery significantly induced the apoptosis of smooth muscle cells in the circulus arteriosus cerebri.No significant difference between anterior/posterior fontanelle injection site on the formation and rupture of intracranial aneurysms in mouse models were observed.Conclusion Arterial ligation surgery can significantly increase the formation and rupture rate of intracranial aneurysms in mouse models,providing a new and reliable animal model for studying the molecular mechanism underlying intracranial aneurysm and drug intervention strategies.

关 键 词：颅内动脉瘤 WILLIS环 小鼠 弹性蛋白酶 

分 类 号：R743.4[医药卫生—神经病学与精神病学]