Survivin、VEGF、Caspase-3在血管瘤不同时期的表达及其相关性研究

Research on Expression and Correlation of Survivin,Vascular Endothelial Growth Factor,and Active Caspase-3 in Different Phases of Hemangiomas

目的研究不同时期的血管瘤组织中,Survivin、VEGF、活化Caspase-3的变化,并对其表达进行相关性分析,探讨其变化对血管瘤病程演化的影响。方法采用免疫组织化学检测Survivin、VEGF、活化Caspase-3在45例血管瘤(增生期30例,消退期15例)和15例正常皮肤组织中的表达。结果①Survivin主要表达在血管瘤内皮细胞胞核中,在增生期、消退期的阳性表达率分别为80%(24/30)和60%(9/15),正常组织中不表达;其表达在血管瘤的增生期、消退期及正常组织的两两比较均有统计学意义。②VEGF主要在血管瘤内皮细胞的胞浆和胞膜中表达,增生期、消退期的阳性表达率分别为90%(27/30)和46.7%(7/15),正常组织不表达;其表达在血管瘤的增生期、消退期及正常组织的两两比较均有统计学意义。③活化Caspase-3主要在血管瘤内皮细胞胞核中表达,在血管瘤增生期、消退期阳性表达率分别为60.0%(18/30)和86.7%(13/15),正常组织中不表达;其表达在血管瘤的增生期、消退期及正常组织的两两比较均有统计学意义。④血管瘤中VEGF的表达与Survivin的表达呈显著正相关(r=0.54,P<0.01);血管瘤中Survivin与活化Caspase-3的表达呈显著负相关(r=-0.51,P<0.01)。结论 VEGF、Survivin抑制Caspase-3的途径可能在血管瘤增生、消退过程中起关键作用,靶向处理该途径有望为血管瘤和各种血管形成性疾病提供新的治疗靶点。

Objective To investigate the expression of survivin, vascular endothelial growth factor （VEGF）, and active caspase-3 in different phases of hemangiomas and analyze their relationship. Methods The samples of 15 normal controls and 45 hemangioma patients （30 proliferating and 15 involuting） were evaluated by immunohistochemistry to determine the expression of survivin, VEGF, and active caspase-3. The data were analyzed by Kuskal-Wallis H test, Mann-Whittney U test, and Spearman rank correlation. The values were considered significant at P〈0.05. Results （1） Survivin mainly localized in nucleus of the endothelial cell. Its positive rates were 80% （24/30） in proliferating hemangioma, 60% （9/15） in involuting hemangioma, and 0 （0/15）, in normal tissue. The difference between proliferating and involuting hemangioma was statistically significant （P〈0.05）, and their differences between the hemangioma groups and normal control group were also significant （P〈0.01）. （2） VEGF mainly expressed in cytoplasm and membrane of the endothelial cell. Its positive rate was 90% （27/30） in proliferative hemangiomas, 46.7% （7/15） in involuting hemangiomas, and 0 （0/15） in normal tissues. The differences between the groups were statistically significant （P〈0.01）. （3） Active caspase-3 mainly located in nucleus of the endothelial cell. Its positive rates were 60% （18/30） in proliferative phase, 86.7%（13/15） in involuting phase, and 0 （0/15） in normal tissue. The difference between proliferating and involuting hemangiomas was statistically significant （P〈0.05）, and the differences between the hemangioma groups and normal control group were also statistically significant （P〈0.01）. （4） VEGF in hemangioma showed positive correlation with survivin （r=0.54, P〈0.01）, while active caspase-3 showed negative correlation with survivin （r=-0.51, P〈0.01）. Conclusion Inhibition of easpase-3 by VEGF/survivin may play a key role in the conversion from proliferating hemangioma to involuting hemangioma. Molecular intervention in the inhibitory path may provide a new strategy for the management of hemangiomas and angiogenesis-dependent diseases.