CAJ | 학술논문

目的观察P选择素在肾病综合征(NS)并发深静脉血栓形成(DVT)中作用,探讨P选择素靶向对比剂及分子磁共振成像(MRI)在DVT犬模型早期诊断应用的可行性.方法 (1)选择我院2005年至2006年间住院NS患者41例,根据核素深静脉造影检查有无伴发DVT,再分为DVT组和无DVT组,检测患者血中P选择素含量.(2)选择健康成年毕格犬,建立DVT模型,并按造模即刻、1 h、3 h采血并取静脉损伤节段,行血管组织和血中P选择素含量检测.(3)利用研制的抗P选择素单抗,制成P选择素靶向对比剂,结合体外犬静脉损伤节段血管MRI,进行犬活体内观察.结果 (1)NS患者血P选择素水平较健康组显著增高(P＜0.01),DvT组又较无伴DVT组明显增高(P＜0.01).(2)模型犬血P选择素水平较对照犬显著增高(P＜0.05),且于受损血管内膜及血栓形成部位明显表达.(3)制备的MRI对比剂,体外可明显增强犬离体受损血管与血栓部位显像信号.体内于犬静脉损伤局部注射对比剂30 min,MRI即显示高于周围肌肉显影的血管信号;1 h可见附壁血栓增强信号;至3 h随血栓形成增大而持续强化,实验组对比度噪声比(CNR)值与对照组比较,差异有统计学意义(11.51±2.32比2.71±O.86,P＜0.01),且显示了与P选择素表达一致的信号强化效果.另从犬损伤部位远心端注射对比剂30 min至1 h,也显示了上述成像效果;2 h至4 h血栓信号由明显上升渐见趋缓,延迟24 h信号强度减弱,实验组CNR值与对照组间差异也有统计学意义(10.40±2.15比1.93±0.57,P＜0.01).此外,该对比剂对实验犬的生命体征及心、肺、肝、肾等脏器均无明显影响.结论 P选择素参与NS合并DVT.利用P选择素单抗MRI对比剂,可在活体内早期定位显像及反映血栓形成状态,为DVT早期诊断提供了一种可行方法.
목적 관찰P선택소재신병종합정(NS)병발심정맥혈전형성(DVT)중작용,탐토P선택소파향대비제급분자자공진성상(MRI)재DVT견모형조기진단응용적가행성.방법 (1)선택아원2005년지2006년간주원NS환자41례,근거핵소심정맥조영검사유무반발DVT,재분위DVT조화무DVT조,검측환자혈중P선택소함량.(2)선택건강성년필격견,건립DVT모형,병안조모즉각、1 h、3 h채혈병취정맥손상절단,행혈관조직화혈중P선택소함량검측.(3)이용연제적항P선택소단항,제성P선택소파향대비제,결합체외견정맥손상절단혈관MRI,진행견활체내관찰.결과 (1)NS환자혈P선택소수평교건강조현저증고(P＜0.01),DvT조우교무반DVT조명현증고(P＜0.01).(2)모형견혈P선택소수평교대조견현저증고(P＜0.05),차우수손혈관내막급혈전형성부위명현표체.(3)제비적MRI대비제,체외가명현증강견리체수손혈관여혈전부위현상신호.체내우견정맥손상국부주사대비제30 min,MRI즉현시고우주위기육현영적혈관신호;1 h가견부벽혈전증강신호;지3 h수혈전형성증대이지속강화,실험조대비도조성비(CNR)치여대조조비교,차이유통계학의의(11.51±2.32비2.71±O.86,P＜0.01),차현시료여P선택소표체일치적신호강화효과.령종견손상부위원심단주사대비제30 min지1 h,야현시료상술성상효과;2 h지4 h혈전신호유명현상승점견추완,연지24 h신호강도감약,실험조CNR치여대조조간차이야유통계학의의(10.40±2.15비1.93±0.57,P＜0.01).차외,해대비제대실험견적생명체정급심、폐、간、신등장기균무명현영향.결론 P선택소삼여NS합병DVT.이용P선택소단항MRI대비제,가재활체내조기정위현상급반영혈전형성상태,위DVT조기진단제공료일충가행방법.
Objectives To detect the effects of P-selectin on deep venous thrombosis (DVT) in nephrotic syndrome (NS). and to evaluate the molecular magnetic resonance imaging (MRI) with a P-selectin targeted conlrost agent in diagnosis of thrombosis in the early phase. Methods (1) Forty-one patients with NS hospitalized in our department from 2005 to 2006 were enrolled in this study. They were assigned into DVT group and non-DVT group according to lower limbs radionuclide imaging (RNV) with 99mTc MAA. Blood P-selectin level was measured by ELISA method. (2) P-selectin was detected both in injured vein and blood immediately, 1 h and 3 h after the dog DVT model was established. (3) The P-selectin-targeted contrast agent was developed by conjugating anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) which was prepared by our lab. The potential of this contrast agent used in vitro molecular imaging experiment as well as in vivo experiment in dog DVT model was investigated. Results (1) Blood P-selectin level was elevated in patients with NS. It was much higher in DVT group than that in non-DVT group. (2) Blood P-selectin level was also elevated in DVT dogs and P-selectin expressed immediately in tunica intima of injured vein and subsequently in thrombus after the model established. (3) Mural thrombus showed higher signal visualization than surrounding muscle in 30 rain after contrast agent injection. These enhanced signals exhibited P-selectin specificity and persisted from the initiation of intima lesions to 3 h after development of thrombosis. There was signficant Differences in contrast-to-noise ratio (CNR) of the experiment group and the control group (11.50±2.32 vs 2.71±0.86, P＜0.01). The same results were derived from 30 rain to 1 hafter contrast agent being injected in distal to heart part of the injured vessel, and the signal decreased 24 h later. Differences in CNR of the experiment group and the control group were also statistically significant (10.40±2.15 vs 1.93±0.57, P＜0.01). Moreover, the contrast agent did not affect the vital signs of the dog. The function of the heart, lung, liver and kidney functions remained normal after contrast administration. Conclusions P-selectin*targeted new MR contrast can be used to early locate thrombus in vivo in an early stage, which does not compromise the function of the important organs. It may become a new method for early diagnosis of thrombosis.