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1、颅内动脉瘤论文：MMP-2、MMP-9及TIMP-1在颅内动脉瘤中的表达及意义【中文摘要】通过观察基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶抑制剂-1(TIMP-1)在颅内动脉瘤中的表达情况,并且与正常颅内动脉的表达相比较,为研究颅内动脉瘤的发病原因及机制提供思路。方法：收集南昌大学第一附属医院2009年10月-2010年7月之间经开颅手术,夹闭动脉瘤后切取的颅内动脉瘤标本31例,其中前交通动脉瘤(ACA)13例,大脑中动脉动脉瘤(MCAA)8例,后交通动脉瘤(PCA)6例,椎动脉动脉瘤(VSA)2例,大脑前动脉动脉瘤2例。正常对照组的16例动脉血管均来

2、自我科同期行颅内血肿清除的脑外伤病人已经离断的动脉血管。其中颞浅7例,脑膜中动脉4例,脑皮层动脉5例。将所得染色标本在光镜下观察颅内动脉瘤壁的镜下病理结构特征。用免疫组化方法比较颅内动脉瘤壁与正常颅内动脉壁中的MMP-2、MMP-9、TIMP-1的表达情况。结果：1.肉眼观察：动脉瘤夹闭前呈浆果状,切除后动脉瘤呈紫褐色、暗红色或灰色。部分动脉瘤瘤腔内有血栓,有些出现机化和钙化。瘤壁厚薄不一,顶部较基底部薄,多数瘤壁由很薄的纤维组织构成,呈半透明状。质地不均,有的松软,有的较硬。2.HE染色：动脉瘤瘤壁很难分辨内膜、中膜和外膜。均丧失了正常脑动脉壁的三层结构。尤其表现在内膜和中膜。内弹力层几乎全

3、部消失,内皮细胞减少,连续性中断。可见血栓形成及部分血栓机化。中膜层正常结构消失,平滑肌萎缩,平滑肌细胞大量减少甚至消失。被大量的纤维组织填充,增生的纤维组织排列紊乱。外膜层较薄,主要为纤维组织,无外弹力层。瘤壁各层均可见到不同程度的炎性细胞浸润,主要为巨噬细胞和淋巴细胞。瘤壁呈现动脉硬化样改变,见细胞内脂质沉积,主要出现在内膜层和中膜层。3.免疫组化染色结果：MMP-2、MMP-9在颅内动脉瘤壁中高表达,分别为87.10%(27/31)、80.65%(25/31),在内、中、外膜均有表达,而对照组中均无表达,差异有统计学意义。TIMP-1在颅内动脉瘤壁和对照组中的阳性率分别为87.10%(2

4、7/31)和56.25%(9/16),差异有统计学意义。结论：1.颅内动脉瘤的病理学改变主要是内弹力层几乎全部消失,平滑肌萎缩,平滑肌细胞大量减少,外膜层较薄,瘤壁各层均可见到不同程度的炎性细胞浸润,主要为巨噬细胞和淋巴细胞。2. MMP-2、MMP-9及TIMP-1在颅内动脉瘤瘤壁各层均有表达,颅内动脉瘤中MMP-2、MMP-9、TIMP-1表达明显增高。3.MMP-2、MMP-9与TIMP-1与颅内动脉瘤密切相关,可能是MMPs与TIMPs共同维系的细胞外基质新陈代谢的动态平衡发生失衡与颅内动脉瘤的发生密切相关,具体机制有待今后进一步的研究。【英文摘要】:To examine the ex

5、pression of matrix metalloproteinases-2 (MMP-2)、matrix metalloproteinases-9 (MMP-9) and Matrix metalloproteinase inhibitor-1 (TIMP-1) in intracranial aneurysms and compare them with those exp ressed in normal brain vessels tissue. To hope to obtain useful informations for better understanding of the

6、 pathogenesis of intracranial aneurysms.Methods:Thirty-one surgical specimens of human cerebal aneurysm in the First Affiliated Hospital of Nanchang University during Oct,2009 to July,2010 were choosen.All specimens were got from dissecting after clinpping the aneurysm in craniotomy.Including 13 of

7、cases anterior communicating aneurysms,8 cases of middle cerebral artery aneurysms,6 cases of posterior communicating aneurysms,2 cases Aneurysm of vertebral artery,2 cases of anterior cerebral artery aneurysms.Sixteen control specimens including 7 cases of superficial temporal artery,4 cases of mid

8、dle meningeal artery, and 5 cases of pial artery.These specimens came from hematoma removal and internal decompression.To observe the expression of MMP-2,MMP-9 and TIMP-1 in human cerebral aneurysm with immunohistochemical method.Results:1.Naked eyes observation:The aneurysms look like berry before

9、clipping.Most specimens were dark brown、dark red and gray.There were thrombosis in some cavities of the aneurysms. Calcification could be seen in some of the aneurysms specimens.The wall of the aneurysms were various,the top were thinner than the basilar part.Most aneurysms were made of thin fibrous

10、 tissue.texture were various,some were soft.and some were stiff.2.HE staining:It is difficult to distinguish the tunica interna、the tunica media and the tunica externa.The three-layered structure of normal brain artery wall were lost. Internal elastic layer almost disappeared,and endothelial cell we

11、re reduced, thrombosis and part organization could be seen.The normal structure of tunica media layer were disapeared. smooth muscle atrophied and smooth muscle cell were reduced even disapeared.were filled with fibrous tissue,and the fibrous tissue arrange disord. Tunica externa layer were thin, ma

12、inly fibrous tissue, no external elastic layer. Inflammatory cell infiltrate could be seen in every layer of the aneurysms wall, mainly macrophages and lymphocytes.The aneurysmal wall showed atherosclerosis-like changes, lipidoses could be seen in the cell,mainly in the tunica interna and tunica med

13、ia.3.The immunhistochemistry staining:The high expression of MMP-2, MMP -9 in human cerebal aneurysmal walls,were 87.10%(27/31) and 80.65% (25/31),MMP-2、MMP-9 expressed in tunica interna、tunica media and tunica externa.But no erpression of MMP-2、MMP-9 in control group, indicating the statistical sig

14、nificance.The positive rate of TIMP-1 in human cerebal aneurismal walls and control group were 87.10%(27/31) and 56.25%(9/16), indicating the statistical significance.Conclusions:1.The pathological changes of intracranial aneurysms mainly internal elastic layer almost disappeared,and endothelial cel

15、l were reduced and Tunica externa layer were thin. Inflammatory cell infiltrate could be seen in every layer of the aneurysms wall. Mainly macrophages and lymphocytes.2.The high expression of MMP-2,MMP-9 and TIMP-1 in human cerebal aneurismal walls,they express in every layer.3.MMP-2,MMP-9 and TIMP-

16、1 were closely related with intracranial aneurysms, maybe MMPs and TIMP common to maintain the homeostasis of extracellular matrix metabolism occurrence imbalance were closely to related intracranial aneurysm. Specific mechanism needs further research.【关键词】颅内动脉瘤 基质金属蛋白酶 基质金属蛋白酶抑制剂【英文关键词】intracranial

17、 aneurysms matrix metalloproteinases tissue inhibitor of metalloproteinases【目录】MMP-2、MMP-9及TIMP-1在颅内动脉瘤中的表达及意义 摘要 3-5 ABSTRACT 5-7 主要英文缩写词索引 9-10 第1章 前言 10-12 第2章 材料与方法 12-15 2.1 实验材料 12-13 2.1.1 标本选择 12 2.1.2 主要仪器 12 2.1.3 主要试剂 12-13 2.2 方法与步骤 13-14 2.2.1 石蜡包埋固定 13 2.2.2 石蜡标本切片 13 2.2.3 HE染色 13-14 2.2.4 免疫组化染色 14 2.3 结果判定标准 14 2.4 统计学分析 14-15 第3章 结果 15-19 3.1. 肉眼观察 15 3.2. HE染色 15 3.3. MMP-2、MMP-9、TIMP-1在颅内动脉瘤和正常动脉中的表达比较 15-19 第4章 讨论 19-22 第5章 结论 22-23 致谢 23-24 参考文献 24-27 附图 27-32 攻读学位期间的研究成果 32-33 综述 33-39 参考文献 37-39