应用自体颈静脉建立巴马小型猪动脉导管未闭模型  

Establishment of patent ductus arteriosus model in Bama miniature pigs using autogenous jugular vein

作　　者：李健[1,2,3,4] 李文超 张凤文 庄东林[1,2,3,4] 魏培坚 李航 张敏 欧阳文斌[1,2,3,4] 潘湘斌 LI Jian;LI Wenchao;ZHANG Fengwen;ZHUANG Donglin;WEI Peijian;LI Hang;ZHANG Min;OUYANG Wenbin;PAN Xiangbin(Department of Structural Heart Disease,National Center for Cardiovascular Disease,Fuwai Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100037,P.R.China;National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine,Beijing,100037,P.R.China;National Clinical Research Center for Cardiovascular Diseases,Fuwai Hospital,Chinese Academy of Medical Sciences,Beijing,100037,P.R.China;Key Laboratory of Innovative Cardiovascular Devices,Chinese Academy of Medical Sciences,Beijing,100037,P.R.China;Children’s Heart Center,Huazhong Fuwai Hospital,Heart Center,Henan Provincial People’s Hospital,Zhengzhou University People’s Hospital,Zhengzhou,450000,P.R.China;National Center for Cardiovascular Disease,Animal Experimental Center of Fuwai Hospital,Chinese Academy of Medical Sciences,Beijing Key Laboratory of Pre-clinical Research and Evaluation for Cardiovascular Implant Materials,Beijing,102300,P.R.China)

机构地区：[1]中国医学科学院北京协和医学院国家心血管病中心阜外医院结构性心脏病中心,北京100037 [2]国家卫生健康委心血管疾病再生医学研究重点实验室,北京100037 [3]国家心血管疾病临床医学研究中心,北京100037 [4]中国医学科学院心血管创新器械重点实验室,北京100037 [5]郑州大学人民医院河南省人民医院心脏中心华中阜外医院儿童心脏病中心,郑州450000 [6]国家心血管病中心中国医学科学院阜外医院动物实验中心心血管植入材料临床前研究评价北京市重点实验室,北京102300

出　　处：《中国胸心血管外科临床杂志》2024年第12期1832-1837,共6页Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

基　　金：中央级公益性科研院所基本科研业务费(2019PT350005);国家自然科学基金(81970444);北京市科技计划(Z201100005420030);国家高层次人才特殊支持计划(2020-RSW02);中国医学科学院医学与健康科技创新工程(2021-I2M-1-065)。

摘　　要：目的探讨应用自体颈静脉建立巴马小型猪动脉导管未闭(patent ductus arteriosus,PDA)模型的方法和可行性,为PDA封堵器研制及先天性心脏病(先心病)相关肺动脉高压研究提供大动物模型。方法选择体重约45 kg雄性巴马小型猪5头,获取自体颈静脉,经戊二醛固定后,吻合至升主动脉和主肺动脉之间制作PDA模型。术后即刻及术后1周行超声心动图检查及心血管造影检查确认PDA通畅情况,术后1周选取2头模型动物行经股静脉PDA介入封堵术,其余动物处死后获取PDA和肺组织行病理学检查。结果5头动物均顺利建立PDA模型,成功率100.0%。术后即刻及术后1周的超声心动图和血管造影均显示PDA血流通畅,苏木精-伊红染色见PDA内皮化良好;术后1周2头动物成功行经股静脉介入封堵治疗;肺组织病理检查示肺小动脉内膜及肌层增厚,肺间质增厚并见中性粒细胞浸润。结论应用自体颈静脉吻合至升主动脉与主肺动脉之间建立PDA的大动物模型安全、可行,该模型可用于PDA介入封堵器材研发和先心病相关肺动脉高压的病理生理研究。Objective To explore the method and feasibility of establishing patent ductus arteriosus(PDA)model in Bama miniature pig by using autologous jugular vein,and to provide a large animal model for the development of PDA occluder and the study of pulmonary hypertension associated with congenital heart disease.Methods Five male Bama miniature pigs weighing about 45 kg were selected to gain the PDA model of the autogenous jugular vein,which was fixed by glutaraldehyde and anastomosed between the ascending aorta and the main pulmonary artery.The patency of PDA was confirmed by echocardiography and angiocardiography immediately and one week after the operation.Two animals were selected to undergo transcatheter closure of PDA via femoral vein 1 week after the operation,and the rest were euthanized to obtain PDA and lung tissue for pathological examination.Results The PDA model was successfully established in all five animals with a success rate of 100.0%.Immediately and 1 week after the operation,echocardiography and angiography showed that PDA blood flow was unobstructed,and hematoxylin-eosin staining showed that PDA endothelialization was good.One week after the operation,two animals were successfully treated with transcatheter femoral vein occlusion.The pathological examination of lung tissue showed thickening of the intima and muscular layer of pulmonary arterioles,thickening of pulmonary interstitium and infiltration of neutrophils.Conclusion It is safe and feasible to establish a large animal model of PDA by using autogenous jugular vein anastomosis between the ascending aorta and the main pulmonary artery.The model can be used for the development of PDA interventional occlusive devices and the pathophysiological study of congenital heart disease-related pulmonary hypertension.

关 键 词：先天性心脏病 动脉导管未闭 介入封堵 肺动脉高压 动物模型 

分 类 号：R541.1[医药卫生—心血管疾病] R-332[医药卫生—内科学]