分化抑制因子1对创伤组织新生血管化的促进作用观察

目的 探讨分化抑制因子1(Id1)对创伤组织新生血管化的促进作用及其机制.方法 经基因鉴定的SD大鼠16只,随机分为非创伤组(即正常对照组,n=4)和创伤组(包括Id1基因敲除组、Id1诱导表达组和Id1正常表达组,n=4).采用MTT法测定Id1对血管内皮细胞Eahy026增殖的影响,实时定量RT-PCR、蛋白免疫印迹技术检测创伤1、24、48、72h后创伤组织中新生血管化标志物血管内皮细胞生长因子(VEGF)、CD105、内皮素-1(ET-1)等的mRNA和蛋白表达变化,并用报告基因技术检测Id1对VEGF、CD105、ET-1基因表达的调控作用.结果 血管内皮细胞模型实验显示转染Id1siRNA后,血管内皮细胞Eahy926增殖明显受到抑制,以72h时最显著(P<0.01);而转染pcDNAId1后,细胞增殖于48h时即增强(P<0.05),以72h时最显著(P<0.01).创伤组Id1基因敲除大鼠VEGF、CD105的mRNA及蛋白表达均受到抑制(P<0.05),且伤后各时间点表达水平无明显变化.Id1诱导表达组24h后大鼠Id1、VEGF、CD105表达均明显增强(P<0.05),于72h达高峰(P<0.01),而ET-1 mRNA水平在伤后24h升高,48h达高峰(P<0.05),72h下降.报告基因检测结果显示,Id1敲除后VEGF、CD105荧光素酶活性明显受到抑制(P<0.05),而Id1基因诱导表达后VEGF、CD105活性明显增强(P<0.01),但Id1对ET-1的表达无明显影响.结论 Id1能有效促进血管内皮细胞Eahy926增殖,调节血管内皮细胞、创伤组织中VEGF、CD105以及ET-1的表达,在组织细胞新生血管化中起重要作用.     

以整合素αvβ3为靶点的肿瘤分子显像及靶向治疗

整合素αvβ3是由两条多肽链组成的跨膜异二聚体糖蛋白,其高表达于肿瘤新生血管内皮细胞和部分肿瘤细胞表面,而在正常血管和组织表面不表达或低表达,其可通过介导细胞黏附来调控肿瘤血管新生,整合素αvβ3能够与体内外含精氨酸－甘氨酸－天冬氨酸序列的物质发生特异性结合。用不同的放射性核素标记,通过PET/CT、SPECT/CT、PET/MRI显像检测肿瘤整合素αvβ3受体的表达水平,在此研究基础上可将其作为肿瘤新生血管显像和肿瘤早期治疗的靶点。现将国内外关于整合素αvβ3靶向药物的设计、放射性核素的选择及相关药物的研究进展等进行综述。     

放射性核素标记RGD序列多肽与整合素αvβ3受体显像的研究进展

整合素主要介导细胞与细胞、细胞与细胞外基质(ECM)之间的相互黏附,对细胞的黏附、增殖、分化、转移、凋亡起到重要的调控作用,在肿瘤的侵袭转移中发挥重要作用.成熟血管内皮细胞和绝大多数正常器官系统中,整合素αvβ3受体表达缺乏或几乎不能被探及,但其在新生血管内皮细胞中有强烈表达,精氨酸-甘氨酸-天冬氨酸(RGD)肽是整合素αvβ3受体的特异性识别位点,因此,将放射性核素标记到含有RGD序列的肽类化合物上,用于整合素αvβ3受体显像,对于肿瘤早期和高特异性定位、定量诊断及治疗都具有重要意义.近年来国内外对RGD肽的标记方法和αvβ3受体显像进行了研究.     

氪激光诱发大鼠脉络膜新生血管的评估方法比较

目的比较荧光素眼底血管造影(FFA)、脉络膜血管铺片和PECAM-1免疫组化标记血管内皮细胞3种方法对于评价大鼠实验性脉络膜新生血管的优缺点.方法氪激光光凝BN大鼠视网膜色素上皮和脉络膜建立脉络膜新生血管动物模型后2周,分别行荧光眼底血管造影(FFA),脉络膜血管铺片检测和PECAM-1免疫组化标记血管内皮细胞,并对得到的结果进行比较,分析.结果光凝后2周,FFA显示光凝区出现大片圆盘状荧光素渗漏;脉络膜血管铺片在低倍镜下可见分布在视神经周围的激光斑处弥漫的高荧光,高倍镜下表现为圆形网状结构;PECAM-1免疫组化标记的内皮细胞分布在瘢痕的中心和周围.环状的内皮细胞增生活跃形成了管腔,光斑内PECAM-1强阳性表达.结论3种方法结合可以细致描述激光光凝后新生血管的发生过程,更为准确地定性定量评价脉络膜新生血管.     

靶向肿瘤新生血管整合素αvβ3受体显像研究现状及进展

恶性肿瘤的生长和转移依赖于肿瘤血管新生,研究发现整合素αvβ3高表达于肿瘤新生血管内皮细胞和部分肿瘤细胞表面,可通过介导细胞粘附来调控肿瘤血管新生,而整合素αvβ3在正常血管和组织表面不表达或呈低水平表达,据此可将其用作肿瘤新生血管显像和治疗的新靶点。近年来国内外关于整合素αvβ3靶向药物的设计、放射性核素的选择以及此类药物的最新研究内容有了较大进展,笔者将对如何更好地设计整合素αvβ3靶向药物、选择合适的放射性核素以及此类药物的研究方向进行综述。     

PAR1与PAR4在肿瘤转移中作用的研究进展

以往研究表明,凝血酶通过其细胞表面的受体--蛋白酶活化受体(protease-activated receptors,PARs)影响肿瘤的转移.PAR1是介导凝血酶促肿瘤转移的主要受体,表达于血管内皮细胞上的PAR1通过影响肿瘤血管新生而促进肿瘤转移.近年来研究发现,PAR1表达于多数肿瘤细胞表面,其表达水平往往预示着该细胞侵袭能力的强弱.PAR4在肿瘤转移中的作用报道较少,仅有的几篇报道提示,PAR4在血管内皮细胞中有表达且在血管发育中起作用,但其是否通过影响肿瘤血管新生而参与肿瘤转移还未见报道.同时,PAR4在肿瘤细胞上的表达仅见于肺癌组织,且其表达水平与肺癌患者的生存直接相关,提示PAR4可能是介导凝血酶影响肿瘤转移的另一重要受体.     

以血管内皮生长因子及其受体为靶向的肺癌放射性核素显像

肺癌的持续生长、侵袭转移与新生血管生成密切相关,在新生血管生成过程中,血管内皮生长因子(VEGF)是作用最强、特异性最高的调控因子.因此,通过对其表达、活性及效应等方面进行有效抑制而达到治疗肺癌的目的 ,是近年来抗肺癌治疗的新方法和手段之一.同时,以VEGF及其受体为靶向的放射性核素显像,不仅可以显示肺癌的血管生成,而且在肺癌的早期诊断、正确分期及预后等方面均具有重要意义.     

靶向超声微泡对结肠癌新生血管分子成像的实验研究

目的 探讨以VEGFR2 (kinase insert domain receptor,KDR)为靶点的靶向超声微泡对裸鼠结肠癌新生血管的成像效果.方法 以生物素-亲和素桥接法将特异性结合VEGF主要受体KDR的小肽K237与脂质微泡耦联构建靶向微泡,用同样方法将对照肽与脂质微泡耦联,构建对照微泡.以KDR阴性表达的人结肠癌LS174T细胞株建立人结肠癌裸鼠移植瘤模型.12只荷瘤鼠经尾静脉随机先后注射靶向微泡、对照微泡,2种微泡注射间隔30 min.注射靶向微泡后5 min和注射对照微泡后5 min荷瘤鼠均行超声造影检查,观察各组微泡在肿瘤组织造影增强情况,测量肿瘤组织的声强度(Ⅵ).另取6只荷瘤鼠预先注射K237肽后再注射靶向微泡,观察微泡的成像效果.靶向微泡组、对照微泡组、小肽预先封闭组肿瘤组织的Ⅵ值比较采用单因素方差分析,组间多重比较采用最小显著性差异t检验.用免疫组织化学技术检测KDR在肿瘤组织表达及分布规律.结果 成功制备了靶向微泡.注射超声微泡后5 min超声检查显示靶向微泡组肿瘤组织超声造影明显增强,对照微泡组及小肽预先封闭组仅见轻度的超声造影增强.3组Ⅵ值差异有统计学意义(F=39.130,P＜0.01).靶向微泡组与对照微泡组Ⅵ值差异有统计学意义(30.18±9.56与8.28±4.74,t=6.91,P＜0.01);小肽预先封闭组Ⅵ值与靶向微泡组差异有统计学意义(9.23±3.44与30.18±9.56,t =4.91,P＜0.01).免疫组织化学结果显示,荷瘤鼠结肠癌新生血管内皮细胞KDR表达较正常组织血管内皮细胞KDR表达显著增加.结论 以KDR为靶点的靶向超声微泡可以与荷瘤鼠肿瘤新生血管内皮特异性黏附并有效评价肿瘤新生血管形成.     

内皮祖细胞在实体瘤治疗中的作用研究进展

1997年,Asahara等[1]运用免疫磁珠分选法首次从成人外周血中分离出了一种CD34＋/VEGFR-2＋、可分化为成熟内皮细胞（endothelial cells,ECs）的单个核细胞,将之命名为内皮祖细胞（endothelial progenitor cells,EPCs）.内皮祖细胞参与胚胎时期血管发生（vasculogenesis）,在成年个体可通过血管发生和血管生成（angiogenesis）两种方式参与血管新生[2-3].     

博莱霉素损伤肺TGF β1与VEGF表达特征与血管新生的关系

目的　研究肺纤维化大鼠的血管内皮细胞生长因子 (VEGF)和转化生长因子 (TGF -β1)的合成和分布规律与血管新生的关系及其在肺纤维化发生、发展过程中的意义。方法　用免疫组织化学的原位杂交方法观察博莱霉素 (BLM )组和对照组在 3d、7d、14d、2 1d、2 8d时肺组织内VEGF和TGF -β1的合成和分布情况 ,并结合透射电镜及光学显微镜观察肺毛细血管的病理变化。 结果　博莱霉素大鼠VEGF与TGF -β1表达早期明显增强并且持续存在 ,两者呈平行增长 ,在肺内间质细胞的表达以 2 8d分布最广 ,其表达区域与血管新生及纤维组织增生区域相吻合。肺毛细血管内皮细胞早期见坏死、脱落、通透性增高 ,此后大量毛细血管新生 ,新生血管扭曲 ,通透性高 ,且可见血管内血栓形成。这种变化在 2 8d组仍然存在。结论　VEGF与TGF -β1的表达与血管新生密切相关 ,这两种因子的持续的高表达可能与新生血管损伤或功能障碍有关 ,进而在肺纤维化中起重要作用     

Stress MR imaging for evaluation of popliteal artery entrapment

The popliteal artery entrapment (PAE) syndrome has been recognized as a cause of arterial occlusion in young people. It is the result of an anomaly of the relationship between the popliteal artery and the gastrocnemius muscle. Eight young healthy volunteers (16 legs) and six patients (10 legs) with suspected PAE underwent magnetic resonance (MR) imaging. Gradient-echo images were obtained in axial planes with the leg at rest and during active plantar flexion against resistance. Imaging at rest allowed identification of PAE signs in only one leg, which had an anomalous medial course of the popliteal artery. In the other cases, only the stress technique was able to show signal loss in the popliteal artery due to muscular compression (two legs) or the presence of accessory muscle slip around the vessel (two legs), as confirmed at surgery. MR imaging is therefore a useful technique for the diagnosis of PAE because of its capability of combining information obtainable with other modalities.     

MR imaging of muscle and tender points in fibromyalgia

Fibromyalgia is a syndrome manifested by chronic, diffuse muscu-loskeletal aching and soreness, palpable muscle tender points, and other symptoms. Standardized clinical diagnostic criteria have recently been developed. Skeletal muscle has been postulated as the end organ in this disease. Biochemical, histologic, electromyographic, and conventional radiographic studies have demonstrated no definitive abnormality. This study sought to establish whether magnetic resonance (MR) imaging could demonstrate any abnormality in these patients. Eighteen patients were entered in the study, 14 of whom were able to complete their examinations. T1 -weighted, T2-weighted, gradient-echo, and STIR (short-tau inversion-recovery) sequences were performed in all patients, with selected patients examined with T1weighted, gadopentetate dimeglu-mine-enhanced sequences. The trapezius and suboccipital regions were imaged in patients who, clinically, had active fibro-myalgia. No abnormalities could be detected. The authors conclude that the conventional MR imaging used in this study was unable to depict any primary skeletal muscle abnormality in fibromyalgia.     

Controversies in cervical spine imaging in trauma patients

No area of emergency radiology has generated as much discussion in recent years as the subject of cervical spine imaging for trauma patients. This review will be in three parts. The first will examine the indications for cervical imaging and will focus on those factors that make patients at high risk or low risk for cervical injury. The second part will discuss the merits of radiography and computed tomography as the main screening diagnostic examination. In addition to the roles of each modality in the evaluation process, such factors as efficacy of diagnosis, time (duration) of study, and cost will be discussed. Finally, the third part will explore the methods currently employed to clear the cervical spine in comatose patients.Presented at the Annual Meeting of the American Society of Emergency Radiology, Las Vegas, Nevada, 22–25 October, 2003     

Uterine contractions: Possible diagnostic pitfall at MR imaging

A total of 206 nongravid patients with various gynecologic problems underwent pelvic magnetic resonance (MR) examinations that included both sagittal T2-weighted and contrast agent–enhanced T1-weighted images. MR images were retrospectively reviewed to identify changes in endometrial configuration on serial images obtained during the same MR examination. In 20 MR examinations (all in women of reproductive age), endometrial distortion due to myometrial bulging was noted on T2-weighted or contrast-enhanced T1-weighted images. It was absent on other MR images obtained at different times. Myometrial bulging exhibited low signal intensity in 18 examinations. The finding resembled adenomyosis or leiomyoma on T2-weighted or contrast-enhanced T1-weighted images. These results evidence the presence of transient myometrial bulging and transient low-intensity myometrium in the nongravid uterus. This phenomenon is thought to represent uterine contraction. Clinicians should be aware of the potential presence of transient low-signal-intensity myometrial bulging that could present diagnostic problems in the normal uterus.     

Brodie Abscess: MR imaging appearance in 10 patients

The magnetic resonance (MR) imaging features of Brodie abscess have not yet been fully evaluated. Ten patients with Brodie abscess, eight of long bone and two of vertebra, were studied with MR imaging. Long bone abscess had a characteristic “target” appearance with four layers: (a) a center with low signal intensity on T1-weighted images and high signal intensity on T2-weighted and STIR (short-inversion-time inversion recovery) images, (b) an inner ring isointense to muscle on T1-weighted images and with high signal intensity on T2-weighted and STIR images, (c) an outer ring hypoin-tense on all images, and (d) a peripheral halo hypointense on T1-weighted images. In six of eight cases, a soft-tissue mass was found. The two vertebral abscesses had a less specific appearance, with low signal intensity on T1-weighted images and high signal intensity on T2-weighted and STIR images. Only the peripheral halo was clearly identified in both cases.     

Dynamic contrast-enhanced MR imaging assessment of vascularized free fibular grafts

Magnetic resonance (MR) imaging may be a noninvasive method for assessing perfusion of vascularized bone grafts placed for treatment of avascular necrosis. One proximal femur of seven beagles was devascularized, with insertion of a vascularized fibular graft. MR imaging at 1 week (seven dogs) and 6 weeks (five dogs) after surgery included pre- and postcontrast spin-echo sequences, unenhanced twodimensional time-of-flight (TOF) vascular imaging, and dynamic gradient-echo imaging during infusion of gadolinium. Relative signal intensity values of selected regions obtained from the dynamic gradientecho images were plotted as percent enhancement versus time. In the operated hip, MR imaging did not show enhancement in six of seven femoral heads and greater trochanters at 1 week after surgery, with similar results after 6 weeks. MR imaging of fibular grafts 6 weeks after surgery showed an initial rapid increase in enhancement and a subsequent slower increase in five of five dogs, although no enhancement was seen in six of seven dogs at 1 week. These findings contrasted with a rapid initial increase in enhancement followed by slow decline in non-operated hips. Two-dimensional TOP imaging did not show the vascular pedicle of the graft in any dog. Findings of radionuclide bone scanning performed 1 week after surgery were consistent with devascularization of the operated femur and fibular graft. However, tetracycline distribution and histologic findings confirmed the viability of five of five grafts within the devascularized femurs 6 weeks after surgery. Thus, dynamic contrast-enhanced MR imaging at 6 weeks after surgery is valuable for assessing vascular bone graft perfusion, while similar imaging at 1 week may suggest otherwise.     

Adrenal tissue characterization with 0.5-T MR imaging: Value of T2*-weighted images

The authors investigated the value of magnetic resonance (MR) imaging at 0.5 T for distinguishing adrenal adenomas from adrenal metastases. The series included 23 adrenal adenomas (18 nonhyperfunctioning, five hyperfunctioning) and 23 adrenal metastases from various organs. Adrenal tumor–liver signal intensity ratios on T1-, T2-, and T2*-weighted images were calculated for adrenal tissue characterization. Adrenal adenomas were more precisely distinguished from adrenal metastases on T2*-weighted images (21 of 23, 91%) than on T2-weighted images (15 of 23, 65%). T1-weighted images were not useful for this distinction. In conclusion, T2*-weighted images were better than routine T2-weighted images for distinguishing adrenal adenomas from adrenal metastases. It can be postulated that the total signal intensity of adrenal adenomas, which contain some fat components, decreased on T2*-weighted images because of an out-of-phase effect.     

Right-side aortic arch with aneurysm of aberrant left subclavian artery: MR imaging appearance.

Reports of aneurysms of the subclavian artery in both normal and anomalous aortic arches have been rare. The authors describe a patient with a right-side aortic arch and an aneurysm of the aberrant left subclavian artery, which, to the authors' knowledge, is a previously unreported association. At presentation, the aneurysm appeared as a calcified left superior mediastinal mass. Magnetic resonance imaging enabled preoperative diagnosis and guided surgical planning.     

MR angiography of congenital heart disease: Value of segmented two-dimensional inflow technique and maximum-intensity-projection display

Magnetic resonance (MR) angiography of the cardiovascular system was evaluated in 41 patients with congenital heart disease by using a two-dimensional (2D) inflow technique based on a magnetization-prepared gradient-echo pulse sequence with segmented k-space data acquisition and electrocardiographic gating at 0.5 T. Inversion and saturation prepulses were used to suppress stationary tissue and enhance intravascular signal. Presaturation slabs were applied where certain vascular structures had to be suppressed. Sequence parameters were optimized by evaluating signal intensity and contrast characteristics for various flip angles and inversion and saturation delay times. The heart and intrathoracic vasculature were encompassed with 40–50 overlapping sections. Both 2D angiograms and maximum-intensity-projection images were evaluated. Combining data sets acquired in the sagittal and transverse orientations provided the most satisfactory information about the pulmonary arteries. The highest signal-to-noise ratios were obtained with a flip angle of 65° and short prepulse delay times. Two-dimensional MR angiography can provide useful diagnostic information but requires a thorough understanding of in-plane and hemodynamically induced signal intensity changes.