^99Tc^m-3PRGD2用于类风湿关节炎血管形成显像的实验研究  

Experimental study of ^99Tc^m-3PRGD2 imaging on the angiogenesis of rheumatoid arthritis

作　　者：武瑜 张国建[2] 王雪梅[2] 邬心爱[1] 赵振峰 张凯秀 贾日东 Wu Yu;Zhang Guojian;Wang Xuemei;Wu Xin＇ai;Zhao Zhenfeng;Zhang Kaixiu;Jia Ridong(Department of Nuclear Medicine,Affiliated People＇s Hospital of Inner Mongolia Medical University,Hohhot 010020,China;Department of Nuclear Medicine,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010059,Chin)

机构地区：[1]内蒙古医科大学附属人民医院核医学科,呼和浩特010020 [2]内蒙古医科大学附属医院核医学科,呼和浩特010059

出　　处：《中华核医学与分子影像杂志》2018年第8期549-553,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：国家自然科学基金（81260224）

摘　　要：目的观察^99Tc^m－3聚乙二醇－精氨酸－甘氨酸－天冬氨酸二聚体（3PRGD2）在类风湿关节炎（RA）大鼠模型中的摄取情况，为该探针在RA早期诊断中的应用提供理论依据。方法将健康雌性SD大鼠分为胶原诱导性关节炎（CIA）组（100只）、骨性关节炎（OA）组（20只）及对照组（20只），利用牛Ⅱ型胶原乳剂免疫诱导的方法建立CIA模型，注射木瓜蛋白酶加左旋半胱氨酸制作OA模型。对各组于造模前、造模后15、30 d行γ显像，以纵隔为非靶区，分析各组大鼠造模前后靶/非靶组织放射性（T/NT）比值的变化。比较各组大鼠造模前后血清血管内皮生长因子（VEGF）、肿瘤坏死因子－α（TNF－α）及αVβ3表达水平。对各组大鼠后足远端趾间关节行病理和免疫组织化学检查。采用单因素方差分析、Pearson相关和Spearman相关分析处理数据。结果造模前CIA组与OA组及对照组大鼠关节部位T/NT比值分别为0.215±0.049、0.210±0.050、0.209±0.051，差异无统计学意义（F＝0.093，P〉0.05）。CIA组造模成功58只。造模后15 d，CIA组与OA组及对照组大鼠关节部位T/NT比值分别为0.405±0.230、0.223±0.045、0.211±0.049，差异有统计学意义（F＝12.601，P〈0.05）。造模后30 d，CIA组与OA组及对照组大鼠关节部位T/NT比值分别为0.572±0.182、0.238±0.045、0.212±0.055，差异有统计学意义（F＝65.147，P〈0.05）。造模后30 d，CIA组大鼠关节部位T/NT比值与血清VEGF、TNF－α、αVβ3水平、病理损伤指数及滑膜组织中VEGF、TNF－α、αVβ3、CD31、CD34表达水平均呈正相关（r值：0.391～0.721，rs值：0.365～0.669，均P〈0.05）。结论^99Tc^m－3PRGD2可被RA模型大鼠的病变关节特异性摄取，在RA早期滑膜新生血管形成显像方面有潜在的应用价值。ObjectiveTo observe the uptake of ^99Tc^m-3 polyethylene glycol Arg-Gly-Asp dimer （3PRGD2） in rat models of rheumatoid arthritis （RA）, in order to provide theoretical foundation for early diagnosis of RA.MethodsThe healthy female SD rats were divided into collagen induced arthritis （CIA） group （n=100）, osteoarthritis （OA） group （n=20） and control group （n=20）. Bovine collagen type Ⅱ emulsion was used for arthritis induction to establish CIA models. OA models were established by injection of L-cysteine and papain. Gamma imaging was performed before and 15 d, 30 d after the model establishment. The mediastinum was selected as non-target （NT） area and the target （T）/NT ratios were calculated. The serum levels of vascular endothelial growth factor （VEGF）, tumor necrosis factor-α （TNF-α）, αVβ3 before and after the model establishment were measured. Pathological and immunohistochemical detection were performed. One-way analysis of variance, Pearson and Spearman correlation analyses were used to analyze the data.ResultsThere were 58 CIA models successfully established. Before the model establishment, T/NT ratios of CIA group, OA group and control group were 0.215±0.049, 0.210±0.050, 0.209±0.051, respectively （F=0.093, P〉0.05）. The T/NT ratios of the above three groups were 0.405±0.230, 0.223±0.045, 0.211±0.049 （F=12.601, P〈0.05） 15 d post-model establishment, and those were 0.572±0.182, 0.238±0.045, 0.212±0.055 （F=65.147, P〈0.05） 30 d post-model establishment. T/NT ratios of CIA group were positively correlated with the levels of serum VEGF, TNF-α, αVβ3, pathological score and the levels of immunohistochemical markers （VEGF, TNF-α, αVβ3, CD31, CD34; r values： 0.391-0.721, rs values： 0.365-0.669, all P〈0.05）.Conclusion ^99Tc^m-3PRGD2 can be specifically up-taken by RA lesions in rat models, thus has the potential in early synovial neovascularization imaging of RA.

关 键 词：关节炎 类风湿 滑膜 新生血管化 病理性 放射性核素显像 精氨酸-甘氨酸-天冬氨酸 大鼠 

分 类 号：R593.22[医药卫生—内科学]