原肌球蛋白4抗体靶向动脉粥样硬化合成型血管平滑肌细胞体内磁共振成像的实验研究  

Anti-tropomyosin-4 antibodies target synthetic vascular smooth muscle cells in atherosclerotic mice during MR imaging

作　　者：夏敏 吴芬 陆文烨 宋梦星 杨雅雯 马占龙[1] Xia Min;Wu Fen;Lu Wenye;Song Mengxing;Yang Yawen;Ma Zhanlong(Department of Radiology,First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,Jiangsu Province,China)

机构地区：[1]南京医科大学第一附属医院放射科,210029

出　　处：《中华老年心脑血管病杂志》2023年第1期66-70,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(81971669)。

摘　　要：目的观察合成型血管平滑肌细胞(VSMC)标记蛋白原肌球蛋白4(TPM-4)在动脉粥样硬化斑块形成过程中的表达变化及分布,探讨靶向合成型VSMC体内MRI的可行性。方法选择雄性载脂蛋白E(apoE^(-/-))小鼠45只为实验组(高脂饲料喂养),雄性6周龄C57BL/6小鼠25只为对照组(普通饲料喂养)。2组小鼠分别于不同时间点取腹主动脉进行苏木精-伊红、免疫组织化学及Masson染色。从实验组随机选取建模成功apoE^(-/-)小鼠各10只分别为靶向探针组[anti-TPM-4-单纯超微超顺磁性氧化铁纳米颗粒(USPIO)]及单纯USPIO组,在探针注射前及注射24 h后采用7.0 T磁共振采集腹主动脉图像,观察信号变化,扫描完成后取腹主动脉标本进行病理学验证。结果对照组小鼠无斑块形成,实验组小鼠不同时间点斑块内均可见TPM-4表达,阳性表达主要在斑块周围及胶原纤维分布区域。斑块内TPM-4和胶原纤维阳性面积与斑块面积呈正相关(r=0.875,P<0.01;r=0.811,P<0.01)。靶向探针组腹主动脉斑块T2WI相对信号改变率达-(73.72±13.12)%,单纯USPIO组相对信号改变率为-(26.74±16.27)%,差异有统计学意义(P<0.01)。普鲁士蓝染色显示,靶向探针组斑块内明显铁颗粒沉积,而单纯USPIO组散在少许铁颗粒。结论anti-TPM-4-USPIO合成探针靶向动脉粥样硬化合成型VSMC体内MRI具有可行性,为早期诊断动脉粥样硬化的相关分子影像学研究及预防急性心脑血管事件提供新的切入点。Objective To observe the expression and distribution of tropomyosin 4(TPM-4),a marker of synthetic vascular smooth muscle cells(VSMC),during the formation of atherosclero-tic plaques,and to explore the feasibility of its antibodies to target synthetic VSMC in in vivo MR imaging.Methods Forty-five male apoE^(-/-)mice(high-fat diet)and 25 male C57 BL/6 mice(normal chow diet)were selected as the experimental group and control group,respectively.The samples of abdominal aorta were taken from the 2 groups at different time points,and then observed with HE staining,immunohistochemical assay,and Masson staining.After successful modeling,10 apoE^(-/-)mice were randomly selected as targeted probe group[anti-TPM-4 antibodies ultrafine superparamagnetic iron oxide nanoparticles(USPIO)]and simple USPIO group.The abdominal aorta images were collected with 7.0 T MR before and 24 h after probe injection,and the changes of abdominal aorta image signals were compared.Then the abdominal aorta samples were harvested for pathological observation.Results There was no plaque formation in the control group.Immunohistochemical staining showed that the expression of TPM-4 in the plaque was observed at different time points in the experimental group,mainly distributed around the plaque and in the area of collagen fiber.The expression level of TPM-4 in the plaque was positively correlated with the area of collagen fiber(r=0.875,P<0.01)and plaque area(r=0.811,P<0.01).The relative signal change rate of T2WI was-(73.72±13.12)%in the targeted probe group and-(26.74±16.27)%in the control group,with statistical difference between the two groups(P<0.01).Prussian blue staining showed that obvious iron deposits were observed in the synthetic VSMC in the atherosclerotic plaques in the targeted probe group,while few iron particles were scattered in the simple USPIO group.Conclusion Anti-TPM-4-USPIO synthetic probe is feasible to target atherosclerotic synthetic VSMC in in vivo MRI imaging,which provides a new entry point for molecular imaging resea

关 键 词：原肌球蛋白 动脉粥样硬化 肌 平滑 血管 肌细胞 平滑肌 磁共振成像 

分 类 号：R543.5[医药卫生—心血管疾病] R445.2[医药卫生—内科学]