MMP9及VEGF诱导血管生成在中耳胆脂瘤增殖中的作用

发布时间：2018-11-16 18:34

【摘要】： 目的: 采用CD105做为微血管标记物,并以Ki-67作为胆脂瘤增殖的指标研究胆脂瘤上皮下结缔组织微血管生成在胆脂瘤增殖中的作用以及MMP9和VEGF在诱导血管生成中的作用,期望有助于揭示胆脂瘤的发病机理,并为其预防和治疗提供理论和临床依据。方法: 通过免疫组织化学染色方法(二步法)检测MMP9、VEGF、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;采用Image-Pro plus6.0图像分析软件读取胆脂瘤标本和外耳道正常皮肤标本MMP9、VEGF蛋白的平均光密度值;计数MVD来评价微血管生成。结果: 1、中耳胆脂瘤组织中见新生的微血管较丰富、密集,且在形态上表现出异常的改变。正常外耳道皮肤组织中的微血管较少,稀疏,没有明显形态学上的改变。45例中耳胆脂瘤组织中的平均MVD为28.3±7.7,10例正常外耳道皮肤平均MVD为6.1±2.5,两组间差异有统计学意义(t=8.905,p0.001)。 2、中耳胆脂瘤组织中Ki-67蛋白的阳性表达率显著高于正常外耳道皮肤(χ2=7.305,P0.01);随着胆脂瘤上皮下结缔组织微血管密度(MVD)的增加,其Ki-67阳性表达率也相应地增加。 3、中耳胆脂瘤组织中VEGF蛋白的平均光密度值为(0.3816±0.04205),正常外耳道皮肤中VEGF蛋白的平均光密度值为(0.2106±0.02105),两组间差异有统计学意义(t=4.804,p0.01);随着VEGF平均光密度值增加,胆脂瘤上皮基质周围微血管密度(MVD)也相应地增加。 4、中耳胆脂瘤组织中MMP9蛋白的平均光密度值为(0.2816±0.04103),正常外耳道皮肤中MMP9蛋白的平均光密度值为(0.2016±0.01803),两组间差异有统计学意义(t=3.184,p0.01);显著高于正常外耳道皮肤,随着MMP9平均光密度值增加,胆脂瘤上皮基质周围微血管密度(MVD)也相应地增加。 5、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、胆脂瘤上皮细胞具有较强的增殖活性;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提供较丰富的血供和营养。 3、MMP9和VEGF蛋白诱导血管生成在中耳胆脂瘤增殖中起重要作用;MMP9和VEGF在诱导胆脂瘤血管生成过程中具有协同作用。
[Abstract]:Objective: to use CD105 as a microvascular marker. Ki-67 was used as the index of cholesteatoma proliferation to study the role of microvascular formation in cholesteatoma and the role of MMP9 and VEGF in inducing angiogenesis in cholesteatoma in order to reveal the pathogenesis of cholesteatoma. And to provide theoretical and clinical basis for its prevention and treatment. Methods: the expression of MMP9,VEGF,Ki-67 and CD105 in 45 cases of middle ear cholesteatoma and 10 cases of normal external auditory canal skin were detected by immunohistochemical staining. Image-Pro plus6.0 image analysis software was used to read the average optical density of MMP9,VEGF protein from cholesteatoma and normal skin samples of external auditory canal and count MVD to evaluate microangiogenesis. Results: 1. The new microvessels in middle ear cholesteatoma were abundant and dense, and showed abnormal morphologic changes. The average MVD of 45 cases of middle ear cholesteatoma was 28.3 卤7.7 and the average MVD of normal skin of external auditory canal was 6.1 卤2.5. The difference between the two groups was statistically significant (t = 8.905, p 0.001). 2the positive expression rate of Ki-67 protein in middle ear cholesteatoma was significantly higher than that in normal skin of external auditory canal (蠂 2 7.305 P 0.01). With the increase of microvessel density (MVD) in subepithelial connective tissue of cholesteatoma, the positive expression rate of Ki-67 in cholesteatoma was also increased. 3. The average optical density of VEGF protein in middle ear cholesteatoma was (0.3816 卤0.04205), and that in normal skin of external auditory canal was (0.2106 卤0.02105). There was significant difference between the two groups (t = 4.804, p0.01). With the increase of average optical density of VEGF, microvessel density (MVD) around the epithelial matrix of cholesteatoma increased accordingly. (4) the average optical density of MMP9 protein in middle ear cholesteatoma was (0.2816 卤0.04103), and that in normal skin of external auditory canal was (0.2016 卤0.01803). There was significant difference between the two groups (t = 3.184, p 0.01). The microvessel density (MVD) around the epithelial matrix of cholesteatoma increased with the increase of the average optical density of MMP9. 5. The correlation analysis showed that VEGF and MMP9 had synergistic effect on angiogenesis (r 0.851P 0.000). Conclusion: 1. Microvascular hyperplasia exists in subepithelial connective tissue of middle ear cholesteatoma. 2. The epithelial cells of cholesteatoma have strong proliferative activity, and the microvascular hyperplasia in the subepithelial connective tissue of cholesteatoma can provide abundant blood supply and nutrition for the abnormal high proliferation of cholesteatoma epithelium. 3Angiogenesis induced by MMP9 and VEGF proteins plays an important role in the proliferation of middle ear cholesteatoma, while MMP9 and VEGF have synergistic effect in inducing angiogenesis of cholesteatoma.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R764.29

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