【作者】 邬尚忠；

【导师】 廖前德；

【作者基本信息】 中南大学 ， 外科学， 2010， 硕士

【摘要】 目的探讨缺氧诱导因子-1α(HIF-1α),血管内皮生长因子(VEGF)和CD105在骨肉瘤中的表达及其与血管生成的关系。方法采用免疫组织化学SP法检测HIF-1α,VEGF和CD105在36例骨肉瘤和10例骨软骨瘤中的表达,并计数CD105标记的微血管密度(MVD),用统计学软件SPSS18.0进行统计学分析。结果1)骨肉瘤中HIF-1α蛋白的阳性表达率41.7%,HIF-1α在骨软骨瘤中未检测到表达。2)骨肉瘤中VEGF蛋白的阳性表达率为63.9%,VEGF在骨软骨瘤中未检测到表达。3)骨肉瘤MVD值显著高于骨软骨瘤MVD值(P<0.05)。4)骨肉瘤Ⅲ期(有转移组)HIF-1α蛋白阳性表达率与Ⅰ、Ⅱ期(无转移组)相比明显升高,有统计学显著性差异(P<0.05)。5)骨肉瘤Ⅲ期(有转移组)VEGF蛋白阳性表达率与Ⅰ、Ⅱ期(无转移组)相比明显升高,有统计学显著性差异(P<0.05)。6)在骨肉瘤外科分期中,Ⅲ期MVD值显著高于Ⅱ期MVD值,Ⅱ期MVD值显著高于Ⅰ期,有统计学显著性差异(P<0.05)。7)在骨肉瘤中,HIF-1α蛋白与VEGF蛋白的表达呈正相关(rs=0.737,P<0.01),HIF-1α蛋白表达与MVD呈正相关(rs=0.556,P<0.01),VEGF蛋白表达与MVD呈正相关(rs=0.778,P<0.01)。结论(1)HIF-1α和VEGF在骨肉瘤中高表达,有转移组骨肉瘤中HIF-1α、VEGF的表达均高于无转移组,和骨肉瘤的侵润转移密切相关。(2)HIF-1α在骨软骨瘤中不表达,在骨肉瘤中高表达,有可能作为判断骨肿瘤良恶性的潜在标志物。(3)骨肉瘤中HIF-1α蛋白的表达和VEGF蛋白表达呈正相关,HIF-1α蛋白阳性表达和MVD正相关,VEGF蛋白阳性表达和MVD正相关,提示在骨肉瘤中HIF-1α可能主要通过VEGF途径促进肿瘤血管生成,在骨肉瘤发展中起重要作用,抑制其表达可能成为抗肿瘤血管生成的新靶点。更多还原

【Abstract】 Objective To investigate the hypoxia-inducible factor-la (HIF-1α), vascular endothelial growth factor (VEGF) and CD 105 expression in osteosarcoma and their relationship with angiogenesis.Methods Immunohistochemical method (SP) was applied to detected the expressions of HIF-1α, VEGF and CD 105 were detected in 36 cases of human osteosarcoma specimen and 10 cases of osteochondroma. We counted microvessel density(MVD) calculated CD105,then used SPSS 18.0 statistics software for analysis.Results 1)HIF-1αprotein expression rate was 41.7% in osteosarcoma, the expression of HIF-1αin osteochondroma was not detected.2) VEGF protein expression rate was 63.9% in Osteosarcoma, the expression of VEGF in osteochondroma was not detected.3)The MVD value of osteosarcoma were significantly higher than that of osteochondroma(P<0.05).4) the expression of osteosarcoma HIF-1αprotein inⅢperiod (metastasis group) was significantly higher than that inⅠ,Ⅱperiod (without metastasis) with statistically significant difference (P<0.05).5) the expression of osteosarcoma VEGF protein inⅢperiod (metastasis group) was significantly higher than that inⅠ,Ⅱperiod (without metastasis) with statistically significant difference (P<0.05).6) The MVD value of osteosarcoma in III period was significantly higher than that in II period(P<0.05).The MVD value of osteosarcoma inⅡperiod was significantly higher than that in I period (P<0.05).7) The expression of HIF-la protein and VEGF protein in osteosarcoma was positively correlated(rs=0.737, P<0.01). The expression of HIF-1αprotein and MVD value in osteosarcoma was positively correlated(rs =0.556, P<0.01). The expression of HIF-la protein and MVD value in osteosarcoma was positively correlated(rs=0.778, P<0.01).Conclusions(1)The proteins of HIF-1αand VEGF had a high expression in osteosarcoma, the expression of HIF-1α, VEGF in Osteosarcoma with metastasis were higher than those without metastasis, which might be involved into the infiltration and metastasis of osteosarcoma.(2)HIF-la is not expressed in osteochondroma but highly expressed in osteosarcoma, it may be a a new marker to judge the potential of benign and malignant bone tumor.(3)The expression of HIF-1αprotein was positively correlated with that of VEGF protein, the expression of HIF-la protein was positively correlated with MVD, the expression of VEGF protein was positively correlated with MVD, Which verificating HIF-la played an important role in the building of osteosarcomas blood vesse] by depending on the expression of VEGF. So it may be a new target for the inhibition of angiogenesis is by restraining the expression of HIF-1α.更多还原