活血化瘀中药联合血管内皮生长因子基因转移促进股骨头坏死处新生血管形成的实验研究

目的:观察活血化瘀中药联合血管内皮生长因子(VEGF)基因转移对促进股骨头缺血坏死处新生血管形成情况。方法:日本大耳兔40只,随机分为对照组、模型组、中药组、基因组和综合组。治疗8周后采用免疫组织化学方法观察股骨头滑膜VEGF阳性细胞率及数字减影血管造影股骨头血管数目改变情况。结果:模型组VEGF阳性细胞表达率减低,与对照组、基因组、综合组比较,差异有显著性意义(P<0.01),与中药组比较,有统计学差异(P<0.05),综合组VEGF阳性细胞表达率较高,与中药组及基因组比较,有统计学差异(P<0.05)。血管数目:在A区,各组与模型组比较,均无统计学差异;在B区,各组较模型组血管数目均有增加,对照组、基因组、综合组与模型组比较,有统计学差异(P<0.05)。综合组与基因组比较有统计学差异(P<0.05),中药组虽然血管数目较模型组多,但是无统计学意义。结论:活血化瘀中药及VEGF基因转移均可促进股骨头缺血坏死处局部新生血管形成和侧支循环的建立,尤以活血化瘀中药联合基因疗法效果为好,为临床应用活血化瘀中药联合基因疗法治疗股骨头缺血性坏死提供实验依据。     

天麻钩藤饮对脑缺血大鼠的神经保护机制研究

目的 观察天麻钩藤饮对脑缺血大鼠学习记忆能力,VEGF及其受体VEGFR-2/FLK-1的影响,探讨天麻钩藤饮的脑保护作用机制.方法 采用大鼠双侧颈动脉永久性结扎制备脑缺血模型,于术后次日开始给予天麻钩藤饮[5g/(kg·d)]灌胃,分别于2周及4周通过Morris水迷宫观察大鼠行为学的改变,免疫组化观察VEGF及FLK-1的改变.结果 模型组大鼠的潜伏期较假手术组明显延长,记忆能力明显下降.治疗组较模型组明显好转,4周较2周更为明显.2周模型组VEGF、FLK-1主要在神经元表达,较假手术组明显增多,4周表达下降;治疗组VEGF、FLK-1在神经元的表达较模型组明显增多,4周仍高表达.结论 该研究提示,天麻钩藤饮可能通过促进VEGF和特异性受体FLK-1的表达,启动神经元保护机制,发挥脑保护作用,改善脑缺血后大鼠的行为学表现.     

体外胰岛素样生长因子结合蛋白-1对人血管内皮细胞生长的抑制作用

目的 观察胰岛素样生长因子结合蛋白-1对人血管内皮细胞的影响及其对胰岛素样生长因子的调节作用。方法 MTT比色法观察IGFBP-1及与IGF-1预混后对脐静脉内皮细胞(ECV304细胞株)生长影响。结果 IGFBP-1对内皮细胞ECV304的生长具有抑制作用且与剂量成正比；预混后各组IGF-1促细胞生长作用明显被抑制。结论 IGFBP-1既可以直接也可以通过调节IGF-1抑制血管内皮细胞生长。     

FAK和VEGF在直肠癌中的表达及其相互关系的研究

目的：检测粘着斑激酶（FAK）和血管内皮生长因子（VEGF）在直肠癌中的表达及其与侵袭和转移的关系，探讨二者的相关性。方法：采用免疫组织化学SABC法，观察86例直肠癌及30例非直肠癌组织中FAK和VEGF的表达情况。结果：FAKVEGF在直肠癌中的阳性率分别为80％和59％。在非直肠癌组织中的阳性表达率分别为10％和13％。FAKF和VEGF在侵及浆膜层直肠癌病例中的表达明显高于未侵五2浆膜层者，二者之间差异性有统计学意义（P〈0．05）；有淋巴结转移组与无淋巴结转移组比较差异有统计学意义（P〈0．05），FAK与VEGF阳性表达呈正相关（p〈0．01）。结论：FAK、VEGF在直肠癌的侵袭和转移中起重要作用，二者在直肠癌中表达升高可以作为预测直肠癌侵袭和转移的指标     

血管内皮生长因子与胸腔积液

血管内皮生长因子（VEGF）是目前已知活性最强、高度特异的血管生长因子。研究表明：VEGF可使血管通透性增加、渗出增多，在促进胸腔积液形成的过程中起重要作用。深入研究VEGF为进一步认识胸腔积液的发病机制及发展新的治疗策略提供了条件。     

Lymphatic vessel density, microvessel density and lymphangiogenic growth factor expression in colorectal cancer

OBJECTIVE: Microvessel density (MVD) has been studied as a prognostic marker in human cancers. Quantification of lymphatic vessel density (LVD) is now possible by using new antibodies. Expression of the lymphangiogenic growth factors, VEGF-C and VEGF-D, is associated with poorer clinicopathological outcomes in various tumours. The aim of this study was to quantify LVD and MVD in colorectal cancer, determine the relationship between LVD, MVD and clinicopathological variables and examine the relationship between LVD and tumour expression of VEGF-C and VEGF-D. METHOD: Thirty primary colorectal cancers were immunostained for CD34, lymph vessel endothelial hyaluronan receptor-1 (LYVE-1), VEGF-A and VEGF-D using standard techniques. LVD and MVD were determined by Chalkley grid counting. Tumours were assessed for the presence or absence of LYVE-1 positive lymphatics at different areas within the tumour and the tumour was scored for VEGF-C and VEGF-D immunostaining intensity at the invading tumour edge. Non-parametric tests were used for statistical analysis and a P-value of <0.05 was taken as significant. RESULTS: Lymph vessel endothelial hyaluronan receptor-1 was an excellent lymphatic vessel marker. Within normal bowel wall, lymphatic vessels were found rarely in the superficial colonic mucosa, but were numerous in the submucosa and muscularis propria. In the majority of tumours, lymphatic vessels were located in the peri-tumoural area, intra-tumoural vessels were sparse and tended to be narrow with closed lumina. At the invading tumour edge, VEGF-C expression was higher (P = 0.028) and VEGF-D expression lower (P = 0.011), in tumours in which lymphatic vessels were present. No significant differences between LVD and any clinicopathological variable or route of metastasis were identified. CONCLUSION: Lymphatic vessel density and MVD can be quantified in colorectal carcinoma using immunohistochemical techniques. The balance between expression of VEGF-C and VEGF-D at the invading tumour edge may enhance lymphatic metastasis, by promoting tumour lymphangiogenesis or by activation of pre-existing lymphatic vessels. No relationship was identified between LVD and clinicopathological variables.     

VEGF参与CoCl2预处理对神经细胞缺氧损伤的保护作用

目的：探讨CoCl2对体外培养分化SH-SY5Y细胞的缺氧损伤保护作用及缺氧诱导基因产物VEGF在其中的作用。方法：分化的SH-SY5Y细胞随机分为对照组、化学缺氧预处理组（预处理组,细胞先用50μM CoCl2预处理3 h,换液后常氧培养1 h,然后在2%的低氧孵箱内缺氧28 h）、缺氧组（无CoCl2预处理过程,其余同预处理组）。用Western Blotting法测细胞VEGF的蛋白表达,RT-PCR测VEGF的mRNA表达,通过乳酸脱氢酶释放率和MTT细胞活力测定判断细胞损伤程度。然后,进一步通过添加VEGF单克隆抗体、重组人VEGF,验证VEGF在化学缺氧预处理组中的保护作用。结果：化学缺氧预处理组细胞VEGF蛋白、VEGF mRNA表达都显著高于缺氧组（P〈0.01）,预处理组细胞较缺氧组细胞存活率高,乳酸脱氢酶释放率减少（P〈0.01）。MTT细胞活力测定显示,40μg/ml VEGF单克隆抗体可抑制预处理的保护作用,而100 ng/ml重组人VEGF可模拟预处理组的保护作用。结论：CoCl2化学预缺氧可保护神经型细胞对缺氧产生耐受,VEGF可能在其中发挥重要的保护作用。     

金属蛋白酶2、血管内皮生长因子和肿瘤抑制因子在人脑胶质瘤中的表达和临床意义

目的:探讨人脑胶质瘤中的金属蛋白酶2(MMP-2)、血管内皮生长因子(VEGF)和肿瘤抑制因子(P16)的表达。方法:应用免疫组化法检测55例胶质瘤组织中的MMP-2、VEGF和P16蛋白的表达,通过原位杂交检测MMP-2 mRNA的表达。结果:胶质瘤的恶性程度与MMP-2、VEGF表达和P16的缺失表达呈正相关,随着胶质瘤的恶性程度的增高而增加。结论:胶质瘤的恶性程度由多种因素决定。胶质瘤中MMP-2含量越高,肿瘤细胞在浸润的过程中突破血脑屏障的能力越强;VEGF的表达增加,肿瘤的血液供应越丰富,恶性程度越高。P16蛋白缺失率高,组织学分化程度低,在一定程度上反映了胶质瘤细胞的恶性生物学行为。     

血浆血管内皮细胞生长因子与肝细胞癌临床特征的相关性

目的通过检测肝细胞癌(HCC)患者肝动脉栓塞术前血浆血管内皮细胞生长因子(VEGF),考察VEGF表达与肿瘤大小、边界、门脉癌栓、远隔转移之间的相关性。方法收集介入治疗前HCC患者46例,VEGF定量检测采用双抗体夹心酶ABC ELISA法。根据血浆VEFG表达水平将患者分为阳性组(32例)和阴性组(14例),对肿瘤大小、边界、门脉癌栓、远隔转移情况进行组间对比。CT和DSA间接门脉造影获得的图像进行对比评估。结果VEGF阳性表达率69.56%(32/46),阴性表达率30.44%(14/46)。VEGF阳性组肿瘤直径>5cm者26例(81.25%),阴性组12例(85.75%),两组间无显著性差异(P>0.05)。CT片上阳性组肿瘤边界清楚15例(46.88%),阴性组边界清楚8例(57.14%),组间无显著性差异。阳性组门脉癌栓发生率62.50%(20/32),阴性组14.29%(2/14),两组间有极显著性差异(P<0.01)。阳性组远隔转移8例;阴性组无远隔转移,经检验P<0.05。结论血浆VEGF高表达可以提示门脉癌栓或远隔转移的存在,而与肿瘤大小、边界无关。血浆VEGF可能成为观察肿瘤门脉癌栓及远隔转移的指标。     

Pathogenesis of diabetic retinopathy and the renin-angiotensin system.

Despite the beneficial effects of good glycaemic control, loss of vision because of diabetic retinopathy (DR) still occurs. Recent studies have suggested that hypertension is a risk factor for the development and progression of DR and that blood pressure reduction can delay the progression of retinopathy. The renin-angiotensin system is activated by chronic hyperglycaemia, and the vitreous fluid level of angiotensin II (AII) is elevated in patients with proliferative diabetic retinopathy and diabetic macular oedema. AII increases vascular permeability and promotes neovascularization. It has been suggested that an autocrine-paracrine relationship may exist between AII and vascular endothelial growth factor in the ocular tissues. Accordingly, angiotensin-converting enzyme inhibitors or AII Type 1 (AT1) receptor blockers may be useful therapeutic agents for preventing the progression of DR.