MMP9及VEGF诱导血管生成在中耳胆脂瘤增殖与侵袭中的作用

Significance of MMP9 and VEGF induced angiogenesisin middle ear cholesteatoma proliferation and aggression

目的探讨基质金属蛋白酶(matrix metalloproteinases,MMP)9及血管内皮生长因子(vascular endothelial growth factor,VEGF)诱导血管生成在中耳胆脂瘤增殖与侵袭中的作用。方法通过免疫组化方法检测MMP9、VEGF、增殖细胞核抗原(Ki-67)和CD105在45例中耳胆脂瘤组织和10例正常外耳道皮肤中的表达。结果 (1)中耳胆脂瘤上皮下结缔组织中平均微血管密度(MVD)高于正常外耳道皮肤,差异有统计学意义(t=8.905,p<0.001);(2)随着胆脂瘤上皮下结缔组织MVD的增加,其Ki-67阳性表达率也相应地增加;(3)中耳胆脂瘤上皮中VEGF和MMP9的平均光密度值高于正常外耳道皮肤,差异有统计学意义(t=4.804,p<0.01;t=3.184,p<0.01);随着MMP9和VEGF平均光密度值增加,胆脂瘤上皮下结缔组织微血管密度(MVD)也相应地增加;(4)相关性分析显示VEGF和MMP9在诱导血管生成过程中具有协同作用(r=0.851,p=0.000)。结论 (1)中耳胆脂瘤上皮下结缔组织中存在微血管增生。(2)胆脂瘤上皮下结缔组织中微血管增生可以为胆脂瘤上皮的异常高度增殖与侵袭提供较丰富的血供和营养。(3)MMP9和VEGF在诱导胆脂瘤血管生成过程中具有协同作用。

Objective To study the significance of MMP9 and VEGF induced angiogenesis in human middle ear cho- lesteatoma proliferation and aggression. Method We examined the expression of VEGF,MMPg,CD105 and Ki-67 by im- munohistochemical staining in 45 middle ear cholesteatoma specimens and 10 external auditory meatus epithelial cell speci- mens. Result （1） The average microvesscl density （MVD） in cholesteatoma subepithelial connective tissue was higher than normal ear canal skin（t=8.905, p〈0.001 ）. （2） With increased mean MVD, the expression of Ki-67 in cholesteatoma speci- mens also increased. （3） The expression of VEGF and MMP9 in cholesteatoma specimens was stronger than that in normal skin epithelial tissues （t=4.804,p〈0.01 ; t=3.184,p〈0.01） ;With increased average optical density values of MMP9 and VEGF proteins, the cholesteatoma subepithelial connective tissue microvessel density （MVD） was correspondingly in- creased. （4） The expression of MMP9 and VEGF in cholesteatoma specimens was positively correlated （r=0.851, p=0.000）. Conclusion （1） Microvascular proliferation is present in middle ear cholesteatoma. （2） Angiogenesis in cholesteatoma sub- epithelial connective tissue can supply increased blood and nutrition to facilitate proliferation and aggression of cholesteato- ma epithelium. （3） VEGF and MMP9 exert a synergistic effect in the induction of angiogenesis.