【作者】 高庆；

【导师】 樊锐太；

【作者基本信息】 郑州大学 ， 肿瘤学， 2010， 硕士

【摘要】 研究MMP-2、MMP-9、TIMP-2在胶质细胞瘤中的蛋白质表达及其意义,探讨MMP-2、MMP-9、TIMP-2与胶质细胞瘤分级的关系及三者之间的相互关系,从而进一步阐明胶质细胞瘤侵袭性的分子机制。MMP-2、MMP-9及TIMP-2的联合检测可能会更有利于对人脑胶质瘤的恶性生物学行为进行评价与判断,为临床提供评价预后、靶向治疗的新思路。材料与方法本实验收集2006年1月至2008年12月郑州大学第一附属医院神经外科脑胶质瘤手术标本58例,按2000年WHO脑肿瘤分类标准分级：低度恶性组30例(Ⅰ级10例；Ⅱ级20例),高度恶性组28例(Ⅲ级15例；ⅣV级13例)。另取同期急性颅脑损伤内减压时切除的正常脑组织8例。应用免疫组化SP法检测了8例正常脑组织、30例低度恶性脑胶质瘤及28例高度恶性脑胶质瘤组织中MMP-2、MMP-9及TIMP-2蛋白的表达。利用SPSS13.0统计软件处理数据,两样本率的比较采用四格表资料x2检验；多样本率的比较采用行列表资料的x2检验；相关性检验用Spearman相关分析。以α=0.05为显著性检验水准。结果1.MMP-2在正常脑组织(A)、低度恶性(B)及高度恶性脑胶质瘤组织(C)中的阳性表达率呈逐渐升高趋势(其阳性率分别为25.00%(2／8),66.67%(20／30)和89.29%(25／28),组间比较(A:B X2=4.498 P=0.034；B：C X@=4.261 P=0.039；C：A X2=13.714 P=0.000)均有显著性差异(P值均<0.05)。2.MMP-9在正常脑组织(A)、低度恶性(B)及高度恶性脑胶质瘤组织(C)中的阳性表达率呈逐渐升高趋势(其阳性率分别为12.50 %(1／8),73.33%(22／30)和96.43%(27／28)),组间比较(A:B X2=9.783 P=0.002；B：C X2=5.893 P=0.015；C：AX2=25.358 P=0.000)均有显著性差异(P值均<0.05)。3.TIMP-2在正常脑组织(A)、低度恶性(B)及高度恶性脑胶质瘤组织(C)中的阳性表达率呈逐渐升高趋势(其阳性率分别为12.50%%(1／8),56.67%(17／30)和85.71%(24／28)),组间比较(A:B X2=4.942 P=0.026; B：C X2=5.893 P=0.015；C：AX2=15.718 P=0.000)均有显著性差异(P值均<0.05)。4.MMP-2蛋白的表达和MMP-9蛋白的表达之间呈正相关关系(RS=0.521p<0.05),MMP-2蛋白表达阳性的病例中MMP-9蛋白的阳性表达率为93.33%(42／45),MMP-2蛋白表达阴性的病例中,MMP-9蛋白的阳性表达率为53.85%(7／13)。5.MMP-2蛋白的表达和TIMP-2蛋白的表达之间呈正相关关系(RS=0.357p<0.05),MMP-2蛋白表达阳性的病例中TIMP-2蛋白的阳性表达率为80.00%(36／45),MMP-2蛋白表达阴性的病例中,TIMP-2蛋白的阳性表达率为38.46%(5／13)。6.MMP-9蛋白的表达和TIMP-2蛋白的表达之间呈正相关关系(RS=0.331p<0.05),MMP-9蛋白表达阳性的病例中,TIMP-2蛋白的阳性表达率为77.55%(38／49),MMP-9蛋白表达阴性的病例中,TIMP-2蛋白的阳性表达率为33.33%(3／9)。结论1.在不同脑组织中,从正常脑组织到低度恶性脑胶质瘤、高度恶性脑胶质瘤,MMP-2、MMP-9及TIMP-2蛋白表达的阳性率均呈逐渐升高趋势,提示MMP-2、MMP-9、TIMP-2蛋白的表达与脑胶质瘤的发生发展有关。2.MMP-2、MMP-9及TIMP-2蛋白的表达与脑胶质瘤的恶性程度呈正相关关系,提示MMP-2、MMP-9、TIMP-2蛋白的高表达均与胶质瘤的恶性程度有关。3.MMP-2和MMP-9蛋白表达之间呈正相关关系,提示二者表达具有一致性,可能在脑胶质瘤的发生、发展中起协同效应。MMP-2与TIMP-2、MMP-9与TIMP-2蛋白表达之间均呈正相关关系,提示TIMP-2在脑胶质瘤表达调高,并随恶性程度升高而表达增强的机制是一种补偿机制。更多还原

【Abstract】 ObjectiveThis study was aimed to investigate the expression of MMP-2(matrix metalloproteinase-2),MMP-9(matrix metalloproteinase-2)and TIMP-2(tissue inhibitor of metalloproteinase-2) in the glioma and normal brain tissue, and to clarify the relationship between MMP/TIMP expressions (MMP-2,MMP-9andTIMP-2) and every grade of glioma. Meanwhile, the relationship between the expression of MMP-2,MMP-9 and TIMP-2 in the combined detection could be good to human malignant glioma to evaluate and judge behavior, to provide for the evaluation of clinical prognosis, targeted therapy of new ideas. Materials and methotisIn this study, collected from January 2006 to December 2008, the First Affiliated Hospital of Zhengzhou University, Neurosurgery,58 cases of surgical specimens of glioma, according to 2000 WHO grading classification of brain tumors: low grade 30 cases (grade 110 cases;gradeⅡ20 cases),28 cases were:high potential malignancy (grade III 15 cases; grade IV 13 cases).Also,there were 8 cases of normal brain tissue taken from decompression operation of acute brain injury. The expression of MMP-2,MMP-9 and TIMP-2 protein were detected using immunohistochemical SP method in 58 cases of brain glioma (30 cases of low potential malignancy,28 cases of high potential malignancy) and 8 cases of normal brain tissue. SPSS 13.0 process data using statistical software, and compare the two sample rate using 2X2 tables analysis and chi-square statistics; Diverse line of this list was used to compare the rate of information x2 test; Correlation test with Spearman correlation analysis.To a=0.05 level for the test of significance. Result1.MMP-2 in normal brain tissue (A), low-grade (B) and highly malignant brain gliomas (C).The positive expression rate was gradually increased (the positive rates were 25.00%(2/8),66.67%(20/30) and 89.29%(25/28)), between the two groups (A:B X2=4.498 P=0.034; B:C X2=4.261 P=0.039; C:A X2=13.714 P=0.000),and was significantly different (P<0.05).2.MMP-9 in normal brain tissue (A), low-grade (B) and highly malignant brain gliomas (C). The positive expression rate was gradually increased (the positive rates were 12.50%(1/8),73.33%(22/30) and 96.43%(27/28)), between the two groups (A: B X2=9.783 P=0.002; B:C X2=5.893 P=0.015; C:A X2=25.358 P=0.000),and was significantly different (P<0.05).3.TIMP-2 in normal brain tissue (A), low-grade (B) and highly malignant brain gliomas (C) The positive expression rate was gradually increased (the positive rates were 12.50%%(1/8),56.67%(17/30) and 85.71%(24/28)), between the two groups (A:B X2=4.942, P=0.026; B:C X2=5.893, P=0.015; C:A X2=15.718,P= 0.000),and was significantly different (P<0.05).4.MMP-2 protein expression and protein expression of MMP-9 positive correlation between the(RS=0.521, P<0.05), MMP-2 protein positive cases in the MMP-9 protein expression rate was 93.33%(42/45), MMP-2 protein negative cases, MMP-9 protein expression was 53.85%(7/13). 5. MMP-2 protein expression and protein expression of TIMP-2 showed a positive correlation between (RS=0.357,P<0.05), MMP-2 protein positive cases in TIMP-2 protein expression was 80.00%(36/45), MMP-2 protein negative cases, TIMP-2 protein expression was 38.46%(5/13).6. MMP-9 protein expression and TIMP-2 protein positive correlation between the expression (RS=0.331,P<0.05), MMP-9 protein expression in positive cases, TIMP-2 protein expression was 77.55%(38/49), MMP-9 protein expression in negative cases, TIMP-2 protein expression was 33.33%(3/9). Conclusions1. In different brain tissue from normal brain tissue to low-grade malignant gliomas, highly malignant glioma, MMP-2, MMP-9 and TIMP-2 protein expression showed a positive rate increased with, suggesting that MMP-2, MMP-9, TIMP-2 protein expression had relitionship with the incidence of glioma development.2. MMP-2, MMP-9 and TIMP-2 protein expression and degree of malignant gliomas were positively correlated, suggesting that MMP-2, MMP-9, TIMP-2 protein expression and high degree of malignancy of glioma about.3. The expression of MMP-2 and MMP-9 protein were positive correlation, suggesting that the expression of consistency between the two may occur in brain gliomas.The development of a synergistic effect.MMP-2 and TIMP-2, MMP-9 and TIMP-2 protein expression showed a positive correlation between, suggesting that TIMP-2 expression increased in glioma, and the degree of malignancy increased with the increase of the mechanism to express akind of compensation mechanism.更多还原