顱內(nèi)動(dòng)脈瘤論文：MMP-2、MMP-9及TIMP-1在顱內(nèi)動(dòng)脈瘤中的表達(dá)及意義

1、.顱內(nèi)動(dòng)脈瘤論文：MMP-2、MMP-9及TIMP-1在顱內(nèi)動(dòng)脈瘤中的表達(dá)及意義【中文摘要】通過(guò)觀察基質(zhì)金屬蛋白酶-2(MMP-2)、基質(zhì)金屬蛋白酶-9(MMP-9)和基質(zhì)金屬蛋白酶抑制劑-1(TIMP-1)在顱內(nèi)動(dòng)脈瘤中的表達(dá)情況,并且與正常顱內(nèi)動(dòng)脈的表達(dá)相比較,為研究顱內(nèi)動(dòng)脈瘤的發(fā)病原因及機(jī)制提供思路。方法：收集南昌大學(xué)第一附屬醫(yī)院2009年10月-2010年7月之間經(jīng)開顱手術(shù),夾閉動(dòng)脈瘤后切取的顱內(nèi)動(dòng)脈瘤標(biāo)本31例,其中前交通動(dòng)脈瘤(ACA)13例,大腦中動(dòng)脈動(dòng)脈瘤(MCAA)8例,后交通動(dòng)脈瘤(PCA)6例,椎動(dòng)脈動(dòng)脈瘤(VSA)2例,大腦前動(dòng)脈動(dòng)脈瘤2例。正常對(duì)照組的16例動(dòng)脈血管均

2、來(lái)自我科同期行顱內(nèi)血腫清除的腦外傷病人已經(jīng)離斷的動(dòng)脈血管。其中顳淺7例,腦膜中動(dòng)脈4例,腦皮層動(dòng)脈5例。將所得染色標(biāo)本在光鏡下觀察顱內(nèi)動(dòng)脈瘤壁的鏡下病理結(jié)構(gòu)特征。用免疫組化方法比較顱內(nèi)動(dòng)脈瘤壁與正常顱內(nèi)動(dòng)脈壁中的MMP-2、MMP-9、TIMP-1的表達(dá)情況。結(jié)果：1.肉眼觀察：動(dòng)脈瘤夾閉前呈漿果狀,切除后動(dòng)脈瘤呈紫褐色、暗紅色或灰色。部分動(dòng)脈瘤瘤腔內(nèi)有血栓,有些出現(xiàn)機(jī)化和鈣化。瘤壁厚薄不一,頂部較基底部薄,多數(shù)瘤壁由很薄的纖維組織構(gòu)成,呈半透明狀。質(zhì)地不均,有的松軟,有的較硬。2.HE染色：動(dòng)脈瘤瘤壁很難分辨內(nèi)膜、中膜和外膜。均喪失了正常腦動(dòng)脈壁的三層結(jié)構(gòu)。尤其表現(xiàn)在內(nèi)膜和中膜。內(nèi)彈力層幾乎

3、全部消失,內(nèi)皮細(xì)胞減少,連續(xù)性中斷?？梢娧ㄐ纬杉安糠盅C(jī)化。中膜層正常結(jié)構(gòu)消失,平滑肌萎縮,平滑肌細(xì)胞大量減少甚至消失。被大量的纖維組織填充,增生的纖維組織排列紊亂。外膜層較薄,主要為纖維組織,無(wú)外彈力層。瘤壁各層均可見到不同程度的炎性細(xì)胞浸潤(rùn),主要為巨噬細(xì)胞和淋巴細(xì)胞。瘤壁呈現(xiàn)動(dòng)脈硬化樣改變,見細(xì)胞內(nèi)脂質(zhì)沉積,主要出現(xiàn)在內(nèi)膜層和中膜層。3.免疫組化染色結(jié)果：MMP-2、MMP-9在顱內(nèi)動(dòng)脈瘤壁中高表達(dá),分別為87.10%(27/31)、80.65%(25/31),在內(nèi)、中、外膜均有表達(dá),而對(duì)照組中均無(wú)表達(dá),差異有統(tǒng)計(jì)學(xué)意義。TIMP-1在顱內(nèi)動(dòng)脈瘤壁和對(duì)照組中的陽(yáng)性率分別為87.10%(

4、27/31)和56.25%(9/16),差異有統(tǒng)計(jì)學(xué)意義。結(jié)論：1.顱內(nèi)動(dòng)脈瘤的病理學(xué)改變主要是內(nèi)彈力層幾乎全部消失,平滑肌萎縮,平滑肌細(xì)胞大量減少,外膜層較薄,瘤壁各層均可見到不同程度的炎性細(xì)胞浸潤(rùn),主要為巨噬細(xì)胞和淋巴細(xì)胞。2. MMP-2、MMP-9及TIMP-1在顱內(nèi)動(dòng)脈瘤瘤壁各層均有表達(dá),顱內(nèi)動(dòng)脈瘤中MMP-2、MMP-9、TIMP-1表達(dá)明顯增高。3.MMP-2、MMP-9與TIMP-1與顱內(nèi)動(dòng)脈瘤密切相關(guān),可能是MMPs與TIMPs共同維系的細(xì)胞外基質(zhì)新陳代謝的動(dòng)態(tài)平衡發(fā)生失衡與顱內(nèi)動(dòng)脈瘤的發(fā)生密切相關(guān),具體機(jī)制有待今后進(jìn)一步的研究?！居⑽恼?To examine the e

5、xpression 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 th

6、e 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 mi

8、ddle 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 fibrou

10、s 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 w

11、ere 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, m

12、ainly 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 me

13、dia.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 si

14、gnificance.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 ce

15、ll 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.【關(guān)鍵詞】顱內(nèi)動(dòng)脈瘤 基質(zhì)金屬蛋白酶 基質(zhì)金屬蛋白酶抑制劑【英文關(guān)鍵詞】intracranial aneurysms matrix metalloproteinases tissue inhibitor of metalloproteinases【目錄】MMP-2、MMP-9及TIMP-1在顱內(nèi)動(dòng)脈瘤中的表達(dá)及意義 摘要 3-5 ABSTRACT 5-7 主要英文縮寫詞索引 9-10 第1章 前言 10-12 第2章 材料與方法 12-15 2.1 實(shí)驗(yàn)材料 12-13 2.1.1 標(biāo)本選擇 12 2.1.2 主要儀器 12 2.1.3 主要試劑 12-13 2.2 方法與步驟 13-14 2.2.1 石蠟