自体骨髓单个核细胞植入对心肌梗死及其边缘区血管生成相关基因表达的影响

目的 探讨骨髓单个核细胞植入心肌梗死及其边缘区对血管生成相关基因表达的影响。方法以冷冻损伤的方法建立新西兰种家兔心肌梗死模型,4周后,将提取分离的骨髓单个核细胞,植入心肌梗死及其边缘区。以基因芯片研究骨髓单个核细胞植入如何调节心肌梗死及其边缘区血管生成相关基因的表达。并以Wwestern blot进一步在蛋白水平上验证基因芯片分析结果。结果骨髓单个核细胞植入心肌梗死及其边缘区后,在心肌梗死区促进15个血管生成相关基因表达上调超过3倍,而在边缘区则多达40个。骨髓单个核细胞植入心肌梗死及其边缘区使血管内皮生长因子、纤维细胞生长因子及血管生长素-Ⅰ等蛋白表达增加,于心肌梗死边缘区作用更加显。结论骨髓单个核细胞植入心肌梗死及其边缘区可以上调多种重要血管生成相关基因的表达。     

类风湿关节炎与滑膜新生血管

类风湿关节炎(RA)是以对称性多关节炎为主要临床表现的异质性、系统性、自身免疫性疾病,多种炎性细胞因子在缺氧环境下相互作用,关节滑膜血管及血管翳形成,进一步侵蚀软骨及软骨下基质,最终导致关节畸形,功能丧失。因此,抑制RA中新生血管可能会成为未来治疗RA的有效策略。该文对近年来生成及抑制新生血管形成的机制研究及治疗靶点予以综述。     

肿瘤血管生成的分子影像学研究进展

肿瘤血管生成与肿瘤的生长、恶变、转移以及患者的预后有着密切的关系,因此,肿瘤的抗血管生成治疗引起了人们的极大兴趣.分子影像学应用高亲和力的分子探针与靶分子特异性结合的原理,可在活体细胞和分子水平上特征性地显示及测量生物机体的生化过程.近年来,分子影像学技术在肿瘤血管生成的可视化及定量研究中取得了一定的进展,有望成为肿瘤早期诊断与靶向治疗评价的重要手段.该文综述了肿瘤血管生成的分子影像学技术的最新进展.     

Quantification of Carotid Plaque Neovascularization Using Contrast-Enhanced Ultrasound With Histopathologic Validation

We sought to evaluate contrast-enhanced ultrasound (CEUS) imaging for the quantification of carotid plaque neovascularization. Seventeen patients underwent carotid endarterectomy after standard ultrasound and CEUS. Semiquantitative and quantitative analyses of contrast enhancement within the plaque were performed using a visual interpretation scale and quantitative analysis software, respectively. Enhancement intensity (dB) was measured at the plaque (EI_plaque). Each specimen was stained with CD34 and CD68 to assess for microvessels and macrophages, respectively. Semiquantitative CEUS analyses were correlated with neovascularization at histology (r = 0.70, p = 0.002). Quantitative analysis was also correlated with neovascularization at histology (EI_plaquer = 0.81, p < 0.001). EI_plaque (r = 0.64, p = 0.01) was correlated with the degree of enhancement as assessed visually. Semiquantitative and quantitative analyses were not correlated with macrophage infiltration at the plaque. Contrast enhancement in the carotid plaque was correlated with neovascularity at the histopathologic exam. Furthermore, semiquantitative and quantitative measurements were highly correlated with each other, suggesting that either can be used to detect intraplaque neovascularization.     

Clenbuterol Plus Granulocyte Colony-Stimulating Factor Regulates Stem/Progenitor Cell Mobilization and Exerts Beneficial Effect by Increasing Neovascularization in Rats With Heart Failure

BackgroundTreatment of beta₂-adrenergic receptor agonists with myeloid cytokines, such as granulocyte colony-stimulating factor (G-CSF) has been reported to enhance stem/progenitor cell mobilization and proliferation in ischemic myocardium. However, whether the combination therapy of G-CSF and clenbuterol (Clen) contributes to improved left ventricular (LV) function remains uncertain. We investigated whether this combination therapy induced bone marrow–derived stem/progenitor cell mobilization, neovascularization, and altered LV function after acute myocardial infarction (MI).Methods and ResultsFollowing MI, rats were treated with single Clen, high-dose Clen, and G-CSF + Clen. We evaluated LV function and remodeling with the use of echocardiography in addition to hemodynamics 3 weeks after MI. Treatment with G-CSF + Clen increased (P < .05), compared with no treatment, LV ejection fraction 46 ± 3% vs 34 ± 2%, LV dP/dt 5,789 ± 394 mm Hg vs 4,503 ± 283 mm Hg, and the percentage of circulating CD34+ cells, appearing to correlate with improvements in LV function.ConclusionsCombination therapy improved LV function 3 weeks after MI, suggesting that G-CSF + Clen might augment stem/progenitor cell migration, contributing to tissue healing. These data raise the possibility that enhancing endogenous bone marrow–derived stem/progenitor cell mobilization may be a new treatment for ischemic heart failure after MI.     

HKD5对人脐静脉内皮细胞游走及血管形成的抑制作用

目的:体外实验研究活化型高分子量激肽原（HKa）轻链富含组氨酸区域5 (HKD5)对人脐静脉内皮细胞（HUVECs）的粘附、游走及血管形成的影响。 方法:体外重组融合蛋白-活化型高分子量激肽原轻链富含组氨酸区域5 (GST-D5H)。WST-1法观察HUVECs细胞粘附能力；用改良Boyden Chamber膜侵袭系统观察HUVECs细胞游走(趋化)；用血管形成实验观察HUVECs细胞形成新生血管能力。 结果:GST-D5H作用后，HUVECs细胞粘贴率降低（P<0.05），游走穿膜细胞数明显低于对照组（P<0.01），诱导内皮细胞形成管腔数及长度均低于对照组（P<0.05）。 结论:GST-D5H能有效抑制HUVECs细胞粘附、游走，使该细胞粘附力降低，迁移性下降及血管形成数目减少或变细。     

左旋精氨酸对糖尿病大鼠烧伤创面血管形成的影响

目的　观察左旋 (L)精氨酸对糖尿病大鼠烧伤创面修复过程中血管形成的影响。 方法雄性SD大鼠 ,设烫伤对照 (A)组、糖尿病烫伤 (B)组、甘氨酸对照 (C)组和L 精氨酸干预 (D)组 ,每组各 2 5只。B、C、D组大鼠通过腹腔注射链脲佐菌素 (STZ)建立糖尿病模型 ,C、D组分别管饲甘氨酸和L 精氨酸 2 0 0mg·kg-1·d-1。8周后取各组大鼠 (每组 5只 )背部皮肤组织测定糖含量。之后各组大鼠给予 2 0 %TBSA深Ⅱ度烫伤 ,于伤后 3、7、14、2 1d测量创面面积 ,计算创面愈合率 ;采用CD34免疫组织化学染色计算微血管密度 (MVD);检测创面组织释放一氧化氮 (NO)、血管内皮生长因子(VEGF)和转化生长因子 (TGF)β1含量。　结果　与B组相比 ,D组大鼠创面愈合率从伤后第 7天起显著增加为 [( 4 4.10± 3.5 0 ) % ,P <0 0 5 ],创面MVD值在伤后各时相点均显著增加 ( P <0 0 5 ),创面组织中释放NO、VEGF和TGF β1量增加 ,皮肤组织糖含量降低为 ( 1.380± 0 .12 0 )mg/g。　 结论L 精氨酸可通过增加NO、VEGF和TGF β1的合成与释放 ,降低皮肤组织糖含量 ,增加糖尿病大鼠烧伤创面的血管形成 ,并促进创面愈合     

兔VX2肿瘤介入治疗前后肿瘤血管生成的多层螺旋CT灌注成像研究

目的 探讨多层螺旋CT（ISCT）灌注成像在定量评价软组织恶性肿瘤介入治疗前后肿瘤血管生成和介入治疗后早期疗效监测中的应用价值。方法 24只成功种植VX2肿瘤的新西兰大白兔，数字表法随机分为介入组和对照组，每组12只，分别于肿瘤种植后第14天、介入治疗后第3天行常规CT平扫和灌注扫描，计算肿瘤组织和正常肌肉组织的血流量（BF）、血容量（BV）、平均通过时间（MTT）和表面通透性（PS）值，分析各参数之间的差异性；并将各灌注参数分别与肿瘤微血管密度（IVD）值和血管内皮生长因子（VEGF）平均吸光度（A）值进行相关性分析。结果 肿瘤种植后第14天，介入组肿瘤BF、BV、MTT、PS值分别为（303．3±69．9）ml·100g^-1·min^-1、（7．02±3．10）ml／100g、（1．99±0．28）s、（65．9±9．4）ml·100g^-1·min^-1，与正常肌肉组织相比[分别为（11．8±5．0）ml·100g^-1·min^-1、（1．04±0．47）ml／100g、（17．92±7．19）s、（13．1±6．4）ml·100g^-1·min^-1]差异有统计学意义（F值分别为4285．82、1867．46、413．04、698．42，P〈0．01）；与对照组肿瘤的各参数值差异无统计学意义（F值分别为2．47、2．03、0．02、0．53，P〉0．05）。介入组肿瘤IVD值和VEGF平均A值分别为（50．1±4．1）个／高倍视野、0．352±0．011，与对照组肿瘤[分别为（50．2±3．7）个／高倍视野、0．352±0．009]差异无统计学意义（F值分别为0．02、0．19，P〉0．05）。介入治疗后第3天（即种植后第18天），介入组肿瘤BF、BY、MTT、PS、MYD值和YEGF平均A值分别为（7．5±24）ml·100g^-1·min^-1、（1．20±0.23）ml／100g、（3．29±0.57）s,（40±1．5）ml·100g^-1·min^-1、（16．0±2．4）个／高倍视野、0．215±0．008，与对照组相比[分别为（390．2±116．3）ml·100g^-1·min^-1、（8．47±2．53）ml／100g、（1．88±0．34）s、（76．9±11．3）ml·100g^-1·min^-1、（84．8±5．6）个／高倍视野、0．366±0．013]差异有统计学意义（F值分别为10166．91、1310．19、272．84、1649．80、1239．72、4168．91，P〈0．01）；与介入治疗前相比，差异也有统计学意义（t值分别为74．53．49．62、-16．82、35．36、50．41、65．64，P〈0．01）。、肿瘤BF、BV、PS值与IVD值和VEGF平均A值呈正相关（r值均〉0．7，P〈0．05）；MTT值与VEGF平均A值呈负相关（r=-0．78，P〈0．05），而与肿瘤IVD值无明显相关性（r=-0．315，P〉0．05）。结论 NSCT灌注成像是一种定量评价肿瘤血管生成、血流灌注及血管通透性改变的功能成像方法，可以无创、准确地对肿瘤介入治疗早期疗效进行定量评价和动态监测。     

眼底血管造影联合频域光相干断层扫描同步检查法对渗出性老年性黄斑变性脉络膜新生血管的诊断价值

Objective To evaluate the diagnostic value of Heidelberg retinal angiography(HRA) combined with optical coherence tomography (OCT) to detect neovascularization (CNV) in exudative age-related macular degeneration (AMD) patients. Methods This is a cross-sectional study of a series of clinical cases. AMD diagnosis was established by international standard vision chart, Slit lamp microscope, direct or indirect ophthalmoscope examination. A total of 50 eyes (42 cases) of exudative AMD received HRA and frequency domain OCT scan. All 50 eyes received fundus fluorescein angiography (FFA) and frequency-domain OCT simultaneously, and among them 15 eyes also received indocyanine green angiography (ICGA) at the same time. FFA and ICGA were carried out by conventional methods, CNV was localized by real-time Localization technology of frequency domain OCT. In the radial and grid-like section from the areas with strong fluorescence, image acquisition settings are 7 μm fault for each frame, 30° intervals for radialsection, 10 vertical and 10 horizontal scan lines for grid-like section. CNV can be divided into 4 types (typical CNV, partial typical CNV, occult CNV, CNV scarring) according to their boundaries demonstrated in FFA. Based on the features of the OCT images, there were 3 types of integrated image (sub-RPE type, sub-retinal type and mixed type). Results CNV was detected in all 50 eyes. There were 4 eyes (8%) of typical CNV, 11 eyes (22%) of partial typical CNV, 32 eyes (64 %, including 27 eyes of RPE detachment and 5 eyes of passive late leakage) of occult CNV and 3 eyes (6%) of CNV scarring. There were 4 eyes (8%) of sub-RPE type (CNV under the RPE light band) , 16 eyes (32%) of sub-retinal type(interrupted light band of RPE and choroid capillary layer) and 30 eyes (60%) of mixed type of integrated image. Conclusion The image integration technology of the HRA and frequency domain OCT system provide a valuable tool to classify and measure CNV, which will benefit the clinical treatment of AMD patients.     

肾母细胞瘤中微血管计数的临床意义

目的：探讨肿瘤内微血管计数（ＭＶＣ）在肾母细胞瘤中的意义。方法：应用免疫组化染色对３８例肾母细胞瘤进行回顾性研究。结果：①预后差的间变型较预后好的各型ＭＶＣ均显著增高（Ｐ＜０．０５），胚芽型较上皮型ＭＶＣ亦显著增高（Ｐ＜０．０５）。②晚期病例较早期者ＭＶＣ显著增高（Ｐ＜０．００１）。③生存组与死亡组ＭＶＣ有显著差异，前者较低（Ｐ＜０．００１）；高ＭＶＣ组较低ＭＶＣ组的生存率明显降低（Ｐ＝０．００１６）。④随肿瘤内炎细胞浸润程度的增加，ＭＶＣ无显著变化（Ｐ＞０．０５）。结论：ＭＶＣ是判断肾母细胞瘤预后一较理想的指标。