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。     

In vivo Analysis of Tumor Vascularization in the Rat

By using transparent chambers in rats, we have directly observed tumor-induced neovascularization in the early stage and the formation of intricate networks in Yoshida rat ascites hepatoma AH109A and Sato lung carcinoma at high magnification. We counted branching point numbers per unit area in the microvascular network with and without tumors in order to clarify the sites from which new vascular sprouts originate. Branching point number per unit area in normal tissue was 13.6 ± 7.4/0.1 mm² in the field near a terminal arteriole, and 12.9 ± 7.3/0.1 mm² in the field distant from a terminal arteriole. There was no significant difference between these two fields in the normal vascular network. On the other hand, in the tumor vascular network, the branching point number in the field near a terminal arteriole was 50.4 ± 12.6/0.1 mm², and 30.1 ± 11.5/0.1 mm² in the field distant from a terminal arteriole. The difference is highly significant ( P <0.001). The frequency with which new capillaries originated from veins and venules was very low. We concluded from these results that the position from which tumor vessels originated was usually the terminal portion of a terminal arteriole.     

重组腺相关病毒介导caveolin-1基因表达抑制肝癌新生血管形成的实验研究

目的 探讨caveolin-1参与肝细胞癌血管生成及影响血管通透性的作用机制.方法 构建肝癌细胞系HepG2裸鼠皮下移植瘤模型,局部注射编码重组可溶性caveolin-1蛋白的重组腺相关病毒载体rAAV-PEG-caveolin-1,观察其对肝癌细胞生长的抑制作用;通过肿瘤微血管密度(microvessel density,MVD)检测肿瘤新生血管的生成;Western blot检测脉管标志蛋白PECAM-1表达改变;FITC标记右旋糖苷测定肿瘤微血管通透性;放射强度测定法检测肝癌组织中eNOS活性,TUNEL法检测caveolin-1对肿瘤细胞的诱导凋亡效应.结果 rAAV-PEG-caveolin-1转染组治疗第14天后,移植瘤的瘤重较对照组和空载体转染组有不同程度的减小(P＜O.05);免疫组化分析及Western blot结果显示rAAV-PEG-caveolin-1转染组较对照组及空载体组MVD及PECAM-1表达显著减少(P＜0.05);FITC-右旋糖苷测定表明rAAV-PEG-caveolin-1可有效降低肿瘤微血管通透性;rAAV-PEG-caveolin-1转染组较对照组及空载体组eNOS活性明显下降(P＜0.05);TUNEL分析显示rAAV-PEG-caveolin-1可诱导肿瘤细胞凋亡.结论 Caveolin-1是血管生成调节的关键分子,能显著抑制肿瘤新生血管的形成,并能有效降低肿瘤微血管的通透性.

Abstract：

Objective To investigate the antitumor effect of the recombined adeno-associated virus encoding caveolin-1 regulated by progression-elevated gene (PEG) promotor on the angiogenesis of implanted human hepatocellular carcinoma(HCC) cell lines in a nude mouse model. Methods HepG2 cells were inoculated subcutaneously into NOD/SCID mice, and animals were treated with rAAV-PEG-caveolin-1 after tumor cell innoculation. The fluorescence ratio of Evans blue to FITC-dextran was used to assess the changes of microvasculature permeability of the tumor. Western blot and immunohistochemical analyses were employed to detect PECAM-1 expression in tumor microvascular endothelium and microvessel density(MVD), respectively; NOS activity was assessed by citrulline generation. Tumor growth was observed and tumor cell apoptosis in tumor tissues were measured by TUNEL. Results Tumor growth was significantly inhibited in mice injected with rAAV-PEG-caveolin-1. The administration of rAAV-PEG-caveolin-1 significantly blocked vascular leakage in the tumor microcirculation. The levels of PECAM-1 protein detected by Western blot were markedly reduced in rAAV-PEG-caveolin-1-treated mice, and there were fewer MVD in tumors from caveolin-1-treated mice, while NOS catalytic activity was much lower in rAAV-PEG-caveolin-1-treated mice compared to the control and empty vector-treated animals. TUNEL demonstrated significant induction of tumor cell specific apoptosis. Conclusions rAAV-PEG-caveolin-1 can reduce tumor progression through blocking microvascular formation by inhibiting eNOS.     

糖尿病视网膜病变46例激光光凝治疗疗效观察

目的探讨激光光凝治疗糖尿病性视网膜病变的治疗效果。方法对我院近4年来46例81眼的糖尿病性视网膜病变行激光光凝治疗后,定期观察视力,眼底及眼底荧光造影检查(3～4月后),记录新生血管、视网膜出血渗出、玻璃体积血等变化情况,观察期4月至2年。结果视网膜光凝治疗后视力变化1月后视力提高>2行,48眼,无变化的有26眼,视力下降>2行,20眼。眼底情况经FFA观察及检眼镜检查,在有效的光凝点数下,81眼中52眼1～2月微血管瘤基本消退,6眼经再次补充光凝后渐消退,8眼无变化,2眼进展为增生期糖尿病性视网膜病变;反复出现小的出血,均经再次补充光凝后于4～8月渐吸收。结论激光光凝是治疗糖尿病性视网膜病变的有效方法。     

小肾癌4D THRIVE动态增强扫描参数与肿瘤血管生成的相关性研究

目的：探讨小肾癌4D THRIVE动态增强扫描参数与肿瘤血管生成的关系。方法：对30例临床疑似小肾癌患者进行4D THRIVE动态增强扫描,分别计算肿瘤感兴趣区（ROI）及瘤周正常肾组织的动态增强参数：最大增强斜率（Smax）、增强峰值（PH）及峰值时间（Tpeak）。病理标本进行免疫组织化学染色,测定微血管密度（MVD）计数和血管内皮生长因子（VEGF）表达,评价小肾癌各动态增强参数与MVD、VEGF的相关性。结果：小肾癌动态增强参数Smax（r=0.707,P＜0.01）、PH（r=0.687,P＜0.01）与MVD表达呈正相关,Tpeak（r=-0.413,P＜0.05）与MVD表达呈负相关。小肾癌MVD计数（63.07±14.73）个/视野,高于瘤周正常肾组织（P=0.002）;67％（20/30）的小肾癌VEGF表达阳性,高于瘤周正常肾组织（P=0.001）。结论：小肾癌4D THRIVE动态增强扫描部分参数与MVD、VEGF相关,在评价小肾癌血管生成方面有重要价值。     

培哚普利对糖尿病大鼠后肢缺血性血管新生的作用及机制探讨

/eNOS/bFGF的激活.