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南京医科大学学报(自然科学版)                                  第44卷第3期
               ·322 ·                     Journal of Nanjing Medical University(Natural Sciences)   2024年3月


             ·基础研究·

              改良球囊损伤联合高脂饮食建立兔腹主动脉粥样硬化模型



              华   芮,李 宸,雍        辉,林清霞,董 舟,吕           展 ,李春坚    *
                                                         *
              南京医科大学第一附属医院心内科,江苏 南京                  210029




             [摘    要] 目的:评估改良球囊损伤联合高脂饮食建立兔腹主动脉粥样硬化模型方法的有效性,并检测早期斑块中免疫清除
              相关蛋白的表达。方法:采用20只新西兰大白兔,随机分为假手术组、经典手术组、改良手术组。假手术组予普通饮食,麻醉、
              切皮、分离股动脉加缝合,但不行球囊损伤。经典手术组和改良手术组予高脂饮食1周后,行腹主动脉球囊损伤术,其中经典
              手术组单向拉动球囊3次,改良手术组反复前后拉动球囊30~40次,术后继续高脂饮食4周。术后4周采用血管内超声检查腹
              主动脉内膜斑块情况,取腹主动脉损伤段行苏木素⁃伊红(hematoxylin⁃eosin,HE)染色和免疫组化检测。结果:术后4周,各组
              体重增加差异无统计学意义。血管内超声显示改良手术组斑块增生显著,管腔狭窄。HE染色显示经典手术组和改良手术组
              均有不同程度的内膜增生,造模成功率均为 100%。与经典手术组相比,改良手术组最大内膜厚度[(174.69±53.76)μm vs.
             (481.50±81.94)μm,P < 0.05]、平均内膜厚度[(77.49±18.02)μm vs.(262.63±53.04)μm,P < 0.05]、内膜中膜面积比[0.39±0.14
              vs. 1.57±0.30,P < 0.05]和血管狭窄比例[(19.04±5.90)% vs.(52.13±11.31)%,P < 0.05]均显著增加,免疫组化提示改良手术组
              较经典手术组巨噬细胞浸润更为显著。相比假手术组和经典手术组,改良手术组增生内膜中抗吞噬蛋白 CD47 表达更为显
              著。结论:改良球囊损伤联合高脂饮食建立兔腹主动脉粥样硬化模型的方法进一步加速了斑块进展,造模更稳定,可靠性更
              高,且在早期斑块中即可观察到显著的坏死细胞清除缺陷。
             [关键词] 动脉粥样硬化;兔;球囊损伤改良术;CD47
             [中图分类号] R543.5                   [文献标志码] A                        [文章编号] 1007⁃4368(2024)03⁃322⁃07
              doi:10.7655/NYDXBNSN230774


              Construction of a rabbit model of abdominal aorta atherosclerosis by a modified balloon
              injury with a high⁃cholesterol diet

                                                                       *
              HUA Rui,LI Chen,YONG Hui,LIN Qingxia,DONG Zhou,LÜ Zhan ,LI Chunjian *
              Department of Cardiology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China


             [Abstract] Objective:To construct a rabbit model of abdominal aorta atherosclerosis by a modified balloon injury with a high ⁃
              cholesterol diet,and evaluate the expression of immune clearance related proteins in early plaques. Methods:A total of 20 New
              Zealand rabbits were assigned randomly to 3 groups:a sham group,a classical intervention group and a modified intervention group.
              The high⁃cholesterol diet and normal diet were given to the intervention groups and the sham group,respectively for one week,after
              which the model was constructed through the femoral artery. The rabbits in the sham group were given a general diet,anesthetized,skin
              cut,isolated femoral artery and sutured,but without balloon injury. For the rabbits in the classic intervention group,a balloon was
              inserted into the abdominal aorta,inflated and unidirectionally pulled 3 times. For the rabbits in the modified intervention group,the
              balloon was inserted,inflated and a bidirectionally pushed and pulled for 30-40 times. Following the intervention,the two intervention
              groups received a high⁃cholesterol diet,while the sham group received a normal diet for another 4 weeks. The intravascular ultrasound
              was performed to examine the abdominal aorta via the femoral artery,and the injured segments of abdominal aorta were sampled for
              further hematoxylin ⁃ eosin(HE)and immunohistochemistry staining at the end of the study. Results:There was no significant
              difference in weight gain measured at 4 weeks post intervention among the 3 groups. The intravascular ultrasound demonstrated
              significant plaque hyperplasia and lumen stenosis in the modified intervention group. HE staining revealed varying degrees of intimal
              hyperplasia in all samples from both intervention groups. Compared with the classical intervention group,the modified intervention

             [基金项目] 国家重点研发计划(2022YFC2402404);中国博士后科学基金面上资助项目(2023M731411)
              ∗
              通信作者(Corresponding author),E⁃mail:lijay@njmu.edu.cn;lvzhan1995@163.com
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