内痔粘膜及血管上皮细胞VEGF/FGF2的表达与内痔分期的相关性分析

目的通过观察人体内痔不同分期粘膜及血管内皮细胞生长因子(VEGF)及碱性成纤维细胞生长因子(FGF2)的表达,探讨内痔的发生及发展机制。方法收集南方医院肛肠科门诊手术切除的Ⅰ、Ⅱ、Ⅲ期内痔标本134例(Ⅰ期42例,Ⅱ期45例,Ⅲ期47例),内痔周围正常肠壁组织40例作为对照,采用HE染色观察组织的病理学变化,采用免疫组织化学方法检测血管内皮细胞VEGF及FGF2的表达。结果正常组及Ⅰ期内痔黏膜层被覆上皮完整,未见扩张血管;Ⅱ期内痔黏膜层被覆上皮破坏,黏膜肌层破坏,黏膜层内见新生血管;Ⅲ期内痔黏膜层被覆上皮破坏,见血管管壁增厚迂曲,管腔扩张;与正常粘膜成纤维细胞相比VEGF在粘膜层成纤维细胞表达水平明显升高,并随分期增高而增高(F=883.961,P<0.01),FGF2也存在相同表达(F=656.013,P<0.01);与正常组相比VEGF在血管内皮细胞表达水平明显升高,并随分期增高而增高(F=776.561,P<0.01),FGF2在血管内皮细胞的表达水平存在相同趋势(F=1066.458,P<0.01)。结论 VEGF及FGF2在内痔的形成过程中具有促进血管内皮细胞和粘膜下成纤维细胞增生的作用,同时可作为内痔发生发展的分子标志物。

Correlation analysis of VEGF/FGF2 expression in the hemorrhoidal mucosa and vascular epithelial cells with hemorrhoids staging

Objective　To investigate pathogenetic mechanism and progression of hemorrhoids at different stages by analyzing the expression of endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2).　Methods　134 hemorrhoids specimen were collected from the out-patients of Nanfang Hospital, and there were 42 cases of hemarrhoids in gradeⅠ, 45 in grade Ⅱ, 47 in grade Ⅲ . Normal tissues of 40 cases among these patients were used as controls. Histopathological changes were obtained from HE stained slide of the disease tissues, as well as the expression of vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (FGF2) with immunohistochemical staining.　Results　The epithelial cells were not injured and intact covering in the mucosa of the normal group and grade Ⅰ hemorrhoids, and no dilated blood vessels were found in these tissues. In grade Ⅱ hemorrhoids, they showed injury of the covering epithelial cells and mucosal muscularis, and neovascularization had been found in the mucosae propria. Grade Ⅲ hemorrhoids showed destructive cells of the covering epithelia in the mucosa, newly formed vessels with thickened wall, tortuous and dilated lumen in the mucosae propria. In comparison with the normal mucosa, expression of VEGF in fibroblasts was significantly increased along with hemarrhoids grading (F=883.961, P<0.01), and so did FGF2 (F=656.013, P<0.01); the same changes were observed with examination of VEGF (F=776.561, P<0.01) and FGF2 (F=1066.458, P<0.01) in vascular endothelial cells. Conclusion VEGF and FGF2 can promote the proliferation of vascular endothelial cells and fibroblasts in the formation of hemorrhoids, and can also be used as progression biomarkers of hemorrhoids.