VEGF抗体靶向血管治疗增生性瘢痕的研究

目的探讨VEGF抗体靶向血管治疗对烧伤后增生性瘢痕的治疗作用。方法将人的增生性瘢痕植入裸鼠肩胛部皮下,建立裸鼠增生性瘢痕移植模型。3周后,用不同剂量血管内皮生长因子单克隆抗体进行瘢痕内注射治疗。治疗3周后解剖取材,通过测量瘢痕的大小观察瘢痕的体积变化,用Masson染色和免疫组化技术观察移植瘢痕胶原和微血管数量的变化。结果与PBS对照组相比,靶向血管治疗3周后,增生性瘢痕的体积明显减小,瘢痕胶原和微血管明显减少。结论VEGF抗体靶向血管治疗具有抑制增生性瘢痕微血管生成、胶原合成及抑制瘢痕生长的作用。     

血管内皮生长因子基因沉默抑制人胶质瘤裸鼠移植瘤生长及血管生成的研究

目的 观察靶向血管内皮生长因子(VEGF)的短发夹RNA(shRNA)对裸鼠人脑胶质瘤中VEGF基因表达的抑制作用.方法 体外培养人脑胶质瘤U251细胞株,建立人脑胶质瘤裸鼠皮下接种模型.将成功造模的30只裸鼠随机分为A、B、C 3组(每组10只),分别给予不同处理.观察肿瘤生长.免疫组织化学检测瘤组织中VEGF蛋白表达及组织内的微血管密度(MVD)改变.结果 治疗5周后,VEGF shRNA组(A组)的肿瘤体积为654.0 mm~3、抑瘤率达65.2%,与空质粒组(B组)1790.4 mm~3、4.7%或PBS组(C组)1880.3 mm~3、0%比较,差异有统计学意义(P<0.05).A组荷瘤组织中VEGF和MVD分别为9.52、22.02,与B组17.18、43.58或C组17.82、45.32比较,差异有统计学意义(P<0.05).VEGF蛋白表达与MVD间存在正相关性(r=0.721,P<0.01).结论 应用RNAi技术沉默VEGF基因能明显抑制人脑胶质瘤细胞株U251裸小鼠移植瘤的生长.     

血管内皮生长因子在胃癌中的表达及其与血管生成和细胞增殖的关系

目的 探讨血管内皮生长因子在胃癌中的表达及其与血管生成、细胞增殖关系。方法 应用免疫组织化学方法检测５０例胃癌标本的ＶＥＧＦ表达情况。结果 ＶＥＧＦ表达与胃癌转移及术后早期复发有关。淋巴结转移组和无转移组ＶＥＧＦ阳性率分别为７０．５９％和３１．２５％,两组差异有极显著性。肿瘤浸润达浆腊和未达浆膜组ＶＥＧＰ阳性率分别为６５．８０％及３３．３３％,差异有显著性。结论检测ＶＥＧＦ表达可作为胃癌的预后指标     

类风湿关节炎中巨噬细胞移动抑制因子对内皮细胞功能及血管内皮生长因子的影响

目的探讨巨噬细胞移动抑制因子（MIF）对类风湿关节炎（RA）滑膜内皮血管生成的影响和作用机制。方法免疫组化检查MIF在RA滑膜组织中的表达;加入MIF或PBS溶液培养人微血管内皮细胞株（HMEC-1）,CCK8法观察细胞的生长差异,磷脂酰丝氨酸凋亡试剂盒（AnnexinV法）检测细胞凋亡,RT—QPCR检测细胞中MIF及VEGF的表达差异。结果MIF在5例RA组织中均阳性表达;加入MIF的细胞株增殖显著较加PBS溶液的快（F=216．93,P〈0．01）,细胞株的凋亡被MIF显著抑制（凋亡率从21．37％降为7．01％（t=13．88,P〈0．01）;处于分裂相的细胞数目较加入PBS的细胞株多（G2期＋S期细胞比例从37．89％升为54．05％,t=5．42,P〈0．01）,在加入MIF的细胞株中VEGF的表达4．62倍高于加入PBS的细胞株（t=7．34,P〈0．01）。结论MIF在RA滑膜组织中表达,并通过提高血管内皮细胞的VEGF而促进RA滑膜血管生成而发挥重要的生理作用。MIF或许是治疗RA进展的药物靶点,有望通过抑制RA患者中MIF的表达从而延缓疾病的进展,改善患者的生活质量。     

Vascular endothelial growth factor (VEGF) gene transfer enhances surgical revascularization of necrotic bone.

Avascular necrosis of bone is a relatively common clinical condition caused by inflammatory conditions, steroid or other drug use, and trauma that affect many different sites in man. Revascularization of the necrotic bone is slow to occur, often resulting in bone resorption and eventual collapse of the involved bone. Rapid revascularization and subsequent bone remodeling may lead to improved outcomes. Surgical revascularization with arterovenous bundles (AV bundles) or vascularized bone grafts results in neoangiogenesis and bone remodeling. Gene transfer of an angiogenic factor to the vessel wall may be an additional strategy to further accelerate this process. In this study, we examined the effectiveness of vascular endothelial growth factor (VEGF) gene transfer to augment surgical revascularization of necrotic bone. An adenoviral vector, either with the VEGF gene (VEGF-A) or identical virus without the cDNA VEGF insert (ADV-DeltaE1) was used to transduce endothelial cells in rabbit saphenous arteries. The artery was then placed with its venae comitantes as an AV bundle into necrotic iliac crest bone in vivo. Angiogenesis in the necrotic bone was quantified by bone blood flow measurement and assessment of vessel density following microangiography. The extent of neoangiogenesis was significantly greater in the VEGF group than the control group at 1 week postoperatively.     

靶向血管治疗增生性瘢痕的实验研究

目的 探讨靶向血管治疗烧伤后增生性瘢痕的可行性和方法。方法 通过建立增生性瘢痕的裸鼠移植模型，使用不同剂量血管内皮生长因子(VEGF)的单克隆抗体，进行瘢痕内注射治疗，观察瘢痕Ⅰ型、Ⅲ型胶原和血管的量以及其超微结构的变化。结果 靶向血管治疗3周后，增生性瘢痕的体积明显减小，瘢痕胶原、血管明显减少，瘢痕内大量成纤维细胞坏死、凋亡，代之成熟的纤维细胞，失去了典型增生性瘢痕的特征。结论 血管内皮生长因子可能对增生性瘢痕中的大量血管新生起支持作用，大量血管对增生性瘢痕的胶原合成可能起着促进作用，针对VEGF的靶向血管治疗可能是治疗增生性瘢痕的的一种有意义的方法。     

血管内皮细胞生长因子对胶质瘤中水孔蛋白4表达的影响

目的探讨血管内皮细胞生长因子（VEGF）对水孔蛋白4在胶质瘤中表达的影响。方法利用已鉴定的经抗性筛选的稳定表达正义／反义VEGF cDNA的C6细胞进行裸鼠皮下接种形成胶质瘤的模型，免疫组织化学方法检测VEGF和水孔蛋白4在不同种植瘤内的表达情况。结果正义VEGF组瘤内VEGF及水孔蛋白4的表达与对照组无明显差异，而反义VEGF组瘤内的VEGF及水孔蛋白4的表达均下调（P〈0．05）。结论VEGF可能通过对水孔蛋白4表达的调控而共同参与胶质瘤水肿的病理生理过程。     

白细胞介素-12抑制裸鼠肝癌Ang-2和血管内皮生长因子表达及其意义

目的　探讨白细胞介素 12抑制裸鼠肝癌中血管生成素 2 (Ang 2 )和血管内皮生长因子(VEGF)基因表达及其意义。方法　将小鼠白细胞介素 12基因转染小鼠肝癌H 2 2细胞后,接种到裸鼠肾包膜下,第11天取出肿瘤组织。通过逆转录 聚合酶链反应(RT PCR)观察实验组和对照组瘤组织中Ang 2和VEGF基因在mRNA水平上的差异。结果　实验组Ang 2和VEGF基因的PCR产物条带亮度均弱于对照组(P <0 .0 5 ) ,实验组Ang 2 (0 .7878±0 .14 71)和VEGF(0 .8867±0 .192 4)基因的PCR产物条带辉度比值低于载体对照组(1.0 3 19±0 .15 74、1.1744±0 .1189)和空白对照组(1.0 3 61±0 .15 3 6、1.1874±0 .175 2 ,P <0 .0 5 )。结论　IL 12抑制Ang 2和VEGF基因在裸鼠肝癌组织中的表达,从而抑制了裸鼠肝癌的血管生成     

联合反义存活素、血管内皮生长因子治疗裸鼠骨肉瘤

目的探讨存活素（Survivin，SVV）、血管内皮生长因子（VEGF）反义寡核苷酸（ASODN）联合治疗裸鼠骨肉瘤。方法构建荷骨肉瘤裸鼠模型，采用瘤内注射给药方式（5mg,／kg体重），以反义SVV、反义VEGF对瘤鼠进行联合干预治疗1周，并与各单药组和空白对照组进行比较，观测各组裸鼠肿瘤生长情况、评估瘤体病理形态，免疫组织化学法检测移植瘤组织SVV、VEGF蛋白表达，DNA末端原位标记法（TUNEL法）检测肿瘤细胞凋亡水平。结果与对照组比较，各治疗组肿瘤生长均不同程度受抑，以联合组最为显著，瘤重仅为（0．52±0．01）g，抑瘤率IR为（42．80±0．88）％；各治疗组肿瘤细胞中SVV、VEGF蛋白表达有所减低，肿瘤细胞出现凋亡坏死改变，其中联合组细胞凋亡指数AI[（27．90±3．66）％]显著高于对照组[（7．10±2．05）％，Χ^2=46．27，P〈0．01]。结论联合应用SVV与VEGFASODN将对裸鼠荷骨肉瘤发挥更强的抗瘤效应。     

以血管内皮生长因子受体为靶点抑制瘢痕血管增生的研究

目的　以血管内皮生长因子受体 2 (VEGFR 2 /KDR)为靶点,观察其抗体对烧伤增生性瘢痕新生血管形成的作用。方法　以人烧伤增生性瘢痕移植于裸鼠建立动物模型。治疗组KDR多抗分为10mg/L和5mg/L两组,以磷酸盐缓冲液(PBS)组和空白对照组作对照,每周2次,治疗1、2、3周分别观察瘢痕体积、组织形态学、微血管定量及Ⅰ、Ⅲ型胶原含量的变化。结果　治疗3周后的瘢痕体积(mm3 )、血管密度(个/mm2 )、Ⅰ、Ⅲ型胶原含量(阳性面积) ,KDR两治疗组均与对照组差异有统计学意义(P <0 .0 5 )。形态学显示瘢痕组织内有大量的血管内皮细胞坏死和血管闭塞,成纤维细胞凋亡,对照组变化不明显。结论　KDR抗体可通过抑制血管的形成治疗增生性瘢痕     

血管内皮细胞生长因子(VEGF)基因转染骨髓间充质干细胞的表达

目的检测兔骨髓间充质干细胞(BMSc)经血管内皮细胞生长因子(VEGF165)基因转染后外源基因的表达，为进一步利用经基因转染的BMSc构建血管化组织工程骨组织打下基础。方法构建VEGF真核细胞表达载体，利用脂质体介导转染兔BMSc，使用原位杂交、免疫组织化学的方法检测VEGF165在BMSc中的表达。结果成功构建VEGF真核细胞表达载体，原位杂交、免疫组化方法显示经基因转染的BMSc中有阳性棕黄色颗粒出现，而未转染组呈现阴性结果。结论采用基因转移技术可以将VEGF转染至．BMSc中，并有外源性基因和蛋白的表达。     

血管内皮生长因子和血小板衍化内皮生长因子的表达在甲胎蛋白阴性肝细胞癌根治性切除术后预后预测中的作用

目的 探讨血管内皮生长因子(VEGF)和血小板衍化内皮生长因子(PD-ECGF)在甲胎蛋白(AFP)阴性肝细胞癌切除术后预后预测中的作用.方法 利用组织微阵列技术(tissue mi-croarray)和免疫组织化学方法回顾性研究200例AFP阴性肝癌患者肿瘤中VEGF及PD-ECGF的表达情况,分析其与肝细胞癌切除术后预后的关系.结果 V EGF及PD-ECGF表达阳性组与相应阴性组患者之间的生存率和无瘤生存率差异无统计学意义(P>0.05),而VEGF及PD-ECGF表达阳性组的术后复发率比相应阴性组显著增高(P<0.05).VEGF和PD.ECGF同时阳性表达组其复发率更显著高于同时阴性组(P<0.01),其生存率和无瘤生存率亦显著降低(P<0.05).结论 对于甲胎蛋白阴性肝癌患者,VEGF和PD-ECGF同时表达阳性提示术后易发生复发,预后不佳.     

碱性成纤维细胞生长因子作用血管内皮细胞后c-myc基因mRNA表达的实验研究

目的探讨碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)促进血管内皮细胞增殖的内在分子生物学机理.方法应用组织细胞培养及分子生物学Northern blot技术,检测经bFGF作用的血管内皮细胞中c-myc基因mRNA的表达情况.结果 bFGF作用血管内皮细胞后c-myc基因mRNA的表达增加(P＜0.05),可在2 h达到高峰,并与bFGF的剂量和作用时间有关.结论 bFGF促进血管内皮细胞增殖、分裂的作用与早期反应基因c-myc的激活与表达密切相关,c-myc基因的参与可能是血管内皮细胞由静止期进入增殖期的启动因素之一.     

Effect of ketoprofen in topical formulation on vascular endothelial growth factor expression and tumor growth in nude mice with osteosarcoma.

OST cells, a low metastatic cell line established from human osteosarcoma, were inoculated under the periosteum of the ossa cranii of nude mice. Four weeks later, tumors were percutaneously treated for an additional 4 weeks with a patch containing either placebo or ketoprofen (KP). In the placebo group, OST cells formed osteoid and invaded the cranial bone. Tumor mass weighed 3.54 g. Approximately 85% of cells within the tumor expressed proliferating cell nuclear antigen (PCNA), indicating that they were proliferating with a high mitotic activity. Many feeder vessels were located within the tumor. The majority of tumor cells expressed intensely vascular endothelial growth factor (VEGF). In the KP group, invasion of OST cells into the cranial bone was suppressed and the tumor mass was 47% of that of the placebo group. Approximately 65% of cells within the tumor were PCNA-negative, indicating that their growth was arrested. There were considerably fewer feeder vessels within the tumor in the KP group than in the placebo group. Only a small number of cells expressed VEGF. Based on these findings, we concluded that topical administration of KP to nude mice with osteosarcoma inhibited VEGF expression, reduced the development of feeder vessels for supply of nutrients and oxygen, and suppressed tumor growth.     

整合素连接激酶对瘢痕成纤维细胞VEGF的调控作用

目的 探讨整合素连接激酶(intergrin-linked kinase,ILK)在人瘢痕成纤维细胞中的表达及对成纤维细胞VEGF的调控作用.方法 8例人增生性瘢痕标本采用组织块法分离培养瘢痕成纤维细胞,选取第5～6代细胞备用.实验分为3组①对照组:不做任何处理,只用含10%FCS的DMEM培养液同步培养;②空质粒组:用空质粒转染人瘢痕成纤维细胞;③ILK cDNA表达质粒转染组:用ILK cDNA表达质粒转染人瘢痕成纤维细胞.首先通过免疫细胞化学染色法检测ILKcDNA转染前后成纤维细胞ILK、VEGF的表达变化;应用实时荧光定量PCR(RT-PCR)及Western blot检测成纤维细胞ILK、VEGF的mRNA和蛋白水平变化;最后采用酶联免疫吸附试验(ELISA法)检测3组成纤维细胞上清液中的VEGF蛋白含量.结果 免疫细胞化学染色结果显示瘢痕成纤维细胞胞浆中ILK表达阳性,VEGF表达不明显,经ILK cDNA转染细胞后ILK与VEGF表达均增强;RT-PCR显示ILK cDNA转染组VEGF mRNA表达(0.338±0.060)均高于对照组(0.022±0.001)和空质粒组(0.028±0.005,P＜0.05);Western blot结果显示ILK cDNA转染组VEGF蛋白表达(0.819±0.019)显著高于对照组(0.607±0.033)和空质粒组(0.591±0.024,P＜0.05);ELISA法检测ILK cDNA转染组的VEGF蛋白含量高于其他两组(P＜0.05).结论 ILK可以上调VEGF mRNA及蛋白水平,并且促进成纤维细胞分泌VEGF,ILK可能通过提高瘢痕成纤维细胞合成分泌VEGF而促进增生性瘢痕血管生成.

Abstract：

Objective To explore the expression of intergrin-linked kinase (ILK) and its effect on VEGF expression in fibroblasts from human hypertrophic scar. Methods Fibroblasts were isolated from hypertrophic scar of 8 patients and cultured in vitro. Then the cells were divided into three groups: ① Cells were cultured only in DMEM containing 10% FCS in the control group; ② Cells were transfected with empty plasmid in the empty plasmid group; ③ Cells were transfected with plasmid experessing ILKcDNA in the ILK cDNA plasmid transfection group. First, the expression of ILK and VECF was observed by immunocytochemistry before and after ILK cDNA transfection. Second, ILK and VEGF mRNA expression was investigated by real-time PCR ( RT-PCR). Third, the protein expression of ILK and VEGF was detected by Western blot. Finally, the protein level of VEGF in supernatant of fibroblasts was measured by ELISA. Results Before ILK cDNA transfection, the expression of ILK was positive and the VEGF expression was weak in cytoplasm of fibroblasts . After ILK cDNA transfection, both the expression of ILK and VEGF was enhanced. The level of VEGF mRNA was significantly higher in ILK cDNA transfection group (0.338 ±0.060) than that in control group (0.022 ±0.001) and empty plasmid group (0.028 ± 0. 005 , P ±0. 05 ). The level of VEGF protein was significantly higher in ILK cDNA transfection group (0. 819 ±0. 019) than that in control group (0. 607 ±0. 033) and empty plasmid group (0. 591 ±0. 024, P ＜0. 05). Secretion of VEGF increased remarkably in ILK cDNA transfection group comparing with the other two groups (P＜0. 05). Conclusions ILK could up-regulate the VEGF mRNA and protein level in human scar fibroblasts. It may play an important role in the angiogenesis in hypertrophic scar.     

光动力治疗裸小鼠胰腺移植癌的实验研究

目的 研究光动力治疗（ＰＤＴ）对胰腺癌的治疗效果,为胰腺癌寻找有效的治疗手段。方法 接种人胰腺癌细胞ＳＷ１９９０于裸小鼠皮下,建立移植癌模型,以血卟淋衍生物（ＨｐＤ）作为光敏剂,采用腹腔和瘤内局部注射两种不同方式给药,继以波长６３２．８ｎｍ的Ｈｅ－Ｎｅ激光照射肿瘤局部,观察光动力治疗后肿瘤的生长速度和组织形态学变化,并测定了肿瘤组织内脂质过氧化产物丙二醛（ＭＤＡ）的含量,对其治疗机制进行了初步探讨     

血管内皮生长因子及其反义寡核苷酸对胶质瘤血管形成的影响

目的　研究血管内皮生长因子 (VEGF)及其反义寡核苷酸 (AODN )对胶质瘤血管形成的影响 ,探讨胶质瘤治疗的新策略。方法　采用链霉菌抗生物素蛋白 过氧化酶免疫组化法 (SP法 ) ,分析 48例脑胶质瘤中VEGF蛋白表达和微血管密度 (MYD)的关系 ;并将传代培养的C6细胞接种于大鼠皮下 ,局部注射VEGF反义寡核苷酸和等量的生理盐水 ,检测肿瘤组织微血管密度的变化。结果　在低、高度恶性星形细胞肿瘤中 ,VEGF阳性率分别为 2 6 .0 9% ( 6 /2 3)、6 4.0 0 % ( 16 /2 5 ) ;MVD分别为 6 .6 9± 4.81、2 3 .6 2± 6 .78;其差异有显著性 (P <0 .0 5 ) ;且VEGF蛋白表达与MVD间明显相关。反义寡核苷酸局部注射后大鼠皮下C6胶质瘤的微血管密度降低 ( 10 .13±0 .85 ) ,与对照组差异有显著性 (P <0 .0 1)。结论　VEGF可促进胶质瘤血管形成和恶性进展 ,其反义寡核苷酸可作为胶质瘤治疗的一种辅助手段。     

Antiangiogenic effect of propranolol on the growth of the neuroblastoma xenografts in nude mice

Background

Propranolol has been reported to display an antiangiogenic effect on infantile hemangiomas and also some adult cancers. Little is known, however, about whether propranolol has such effect on pediatric malignancies.

Methods

Nude mice bearing BE(2) C neuroblastoma xenografts were injected intraperitoneally with propranolol and divided into groups of PROP-2 (n = 11), -5 (n = 11), and -10 (n = 10) according to the treating dosages of 2, 5, and 10 mg kg^− 1 day^− 1, respectively. The tumor volume and body weight were recorded every other day. All mice were sacrificed on day 9, and the levels of angiogenic factors were measured in harvested xenografts by immunohistochemistry and western blotting.

Results

The tumor volume and weight of PROP-2 (0.72 ± 0.28 cm³, 0.59 ± 0.21 g) and PROP-5 (0.81 ± 0.35 cm³, 0.61 ± 0.25 g) were significantly decreased when compared with those of CTL (1.22 ± 0.58 cm³, 0.93 ± 0.15 g; P < 0.01). The tumor microvessel density (MVD) scores that PROP-2, -5, and -10 groups had (49.28 ± 17.53, 52.45 ± 17.11, and 51.09 ± 13.18 pixels per picture, respectively) were lower than those from the control group (65.29 ± 17.33 pixels per picture, P < 0.01). Furthermore, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), and metalloproteinase-9 (MMP-9) levels were significantly lower in the groups with propranolol treated dosage of 5 and 10 mg kg^− 1 day^− 1 than in the control group.

Conclusions

Propranolol can exhibit an inhibitory effect on the tumor growth and angiogenic factors expression in neuroblastoma xenografts, which may provide some knowledge to the role of β-blockers in the management of NB.     

血管内皮生长因子在胰腺癌中的表达及其对预后的影响

目的:研究胰腺癌组织中血管内皮生长因子表达与微血管生成和血管侵犯之间的联系,以及其临床意义和对预后的影响。方法:应用免疫组化方法测定36例胰腺癌切除标本中血管内皮生长因子(VEGF,VEGF-C)的表达;通过CD34染色测定其微血管密度(MVD)。结合临床病理和随访资料分析MVD、VEGF、VEGF-C表达与病人预后之间的关系。结果:胰腺癌组织中的MVD为44.04±12.80,VEGF阳性组MVD(49.95±9.57)显著高于阴性组(30.6±18.24)。VEGF的阳性率为69.4%(25/36),发生胰外侵犯组的阳性率为83.3%(20/24),UICC临床分期Ⅲ～Ⅳ期组的阳性率为92.9%(13/14)。VEGF-C的阳性率为55.6%(20/36),淋巴转移组的VEGF-C阳性率为83.3%(10/12),UICC临床分期Ⅲ～Ⅳ组阳性率为85.7%(12/14)。Kaplan-Meier生存分析显示,VEGF、VEGF-C阳性组的预后较差(P<0.05)。结论:胰腺癌的MVD显著升高,VEGF在胰腺癌中的高表达可反映肿瘤微血管生成状况,与胰腺癌的胰外侵犯及UICC临床分期之间有显著意义,故可作为判断预后的依据;VEGF-C与淋巴转移和UICC临床分期相关,也是判断预后的依据。     

血管内皮生长因子和促血管生成素及其受体Tie2在肝细胞癌发生发展中的作用

目的探讨血管内皮生长因子(VEGF)和促血管生成素(Angiopietin)及其受体Tie2在启动肝细胞癌(HCC)血管生成中的调控机制及在HCC发生发展中的作用。方法新鲜HCC标本及癌旁肝组织38例,用实时定量逆转录-聚合酶链反应(RT-PCR)的方法检测Ang-1、Ang-2、Tie2和VEGF在各组织标本中的表达,以CD34标记新生血管内皮并计数微血管密度(MVD),分析上述因子在HCC组织和非癌肝组织中的表达差异、相互作用及其与MVD、临床病理特征之间的关系。结果Ang-1、Tie2在HCC和非癌肝组织中的表达差异无统计学意义(0．194 7±0．086 2比0．232 6±0．109 8,1．601 6±0．900 7比1．340 0±0．703 7,P均>0．05),而VEGF和Ang-2在HCC组织的表达高于非癌肝组织(1．038 0±0．572 0比0.832 3±0．182 4,0．621 3±0.417 6比0．442 9±0．330 1,P均<0．05);VEGF、Ang-2、Ang-2／1都与MVD和临床病理特征相关(P<0．01),但与组织分化程度无关(P>0．05)。结论Ang-2／1的失衡表达及其与VEGF和Tie2的共同作用是启动肝组织血管生成并诱发HCC发生、发展的重要因素;这种因素在HCC中的持续作用进一步促进了肿瘤血管生成和恶性生物学行为。