本文選題：顱內(nèi)動(dòng)脈瘤 + 發(fā)病機(jī)制��； 參考：《四川醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的:1.觀察人顱內(nèi)動(dòng)脈瘤瘤壁的組織病理學(xué)改變;2.檢測(cè)干擾素/維甲酸聯(lián)合誘導(dǎo)細(xì)胞凋亡相關(guān)基因19(gene associated with retinoidinterferon-induced mortality-19,GRIM-19)在顱內(nèi)動(dòng)脈瘤瘤壁中膜平滑肌細(xì)胞中的表達(dá)情況,探討顱內(nèi)動(dòng)脈瘤瘤壁中膜平滑肌細(xì)胞減少的原因及可能機(jī)制及其在顱內(nèi)動(dòng)脈瘤發(fā)生、發(fā)展中的作用。方法:收集整理四川醫(yī)科大學(xué)附屬醫(yī)院神經(jīng)外科于2013年1月~2014年4月收治的顱內(nèi)動(dòng)脈瘤所致蛛網(wǎng)膜下腔出血的病例,選擇經(jīng)開(kāi)顱顯微手術(shù)夾閉顱內(nèi)動(dòng)脈瘤瘤頸后切除瘤囊獲得的45例病理標(biāo)本,并將其歸為動(dòng)脈瘤組,其中男16例,女29例。對(duì)照組為四川醫(yī)科大學(xué)附屬醫(yī)院神經(jīng)外科同期收治的顱腦外傷患者,經(jīng)顱內(nèi)血腫清除術(shù)或內(nèi)減壓術(shù)收集的45例正常顱內(nèi)小動(dòng)脈,其中男27例,女18例。兩組標(biāo)本均要求在保證手術(shù)及患者安全的情況下獲得,手術(shù)前簽知情同意書(shū)。對(duì)兩組標(biāo)本分別進(jìn)行肉眼大體觀察;制備切片行光鏡檢查兩組標(biāo)本組織結(jié)構(gòu);RT-PCR技術(shù)、免疫組化SP法檢測(cè)GRIM-19在顱內(nèi)動(dòng)脈瘤瘤壁及正常血管壁中膜平滑肌細(xì)胞中的表達(dá)情況,比較二者的變化。所有病例排除高血壓、糖尿病等病史者。結(jié)果:1.肉眼大體觀察:動(dòng)脈瘤組標(biāo)本瘤體大多呈暗紅色、棕褐色,囊狀或梭形外觀,大多質(zhì)韌,切開(kāi)瘤體,12例標(biāo)本瘤壁可見(jiàn)表面白色或暗紅色的扁平狀、圓形或橢圓形動(dòng)脈粥樣硬化斑塊,28例標(biāo)本瘤腔內(nèi)有附壁血栓,血栓質(zhì)地較軟。其瘤壁厚度從瘤頸開(kāi)始逐漸變薄,瘤頂最薄者僅殘存薄層纖維膜,甚至有的已經(jīng)破裂。觀察見(jiàn)所有破裂動(dòng)脈瘤,破口均在瘤頂或近瘤頂處。對(duì)照組標(biāo)本血管呈鮮紅色,管腔未見(jiàn)明顯動(dòng)脈粥樣硬化斑塊及附壁血栓。2.光鏡觀察:HE染色:正常顱內(nèi)小動(dòng)脈切片光鏡下見(jiàn)管壁厚薄均勻,內(nèi)、中、外三層膜解剖結(jié)構(gòu)清晰完整無(wú)破壞,各層細(xì)胞形態(tài)正常,相鄰細(xì)胞的肌膜常都形成緊密連接,中層平滑肌細(xì)胞呈同心層結(jié)構(gòu)排列,管壁炎性細(xì)胞少見(jiàn)。動(dòng)脈瘤組切片光鏡下見(jiàn)管壁厚薄不均,從瘤頸開(kāi)始到瘤頂逐漸變薄,部分瘤壁局部或全層向外膨出,三層膜解剖結(jié)構(gòu)不清,瘤壁內(nèi)細(xì)胞部分或全部破壞,炎性細(xì)胞浸潤(rùn)且分部彌漫,可見(jiàn)脂類(lèi)物質(zhì)及膽固醇結(jié)晶沉積,部分瘤壁可見(jiàn)機(jī)化的血栓或粘附于囊內(nèi)壁的新鮮血栓,中層平滑肌細(xì)胞減少。免疫組化染色:GRIM-19在42例顱內(nèi)動(dòng)脈瘤瘤壁中膜平滑肌細(xì)胞中的陽(yáng)性表達(dá)率為93.33%(42/45),GRIM-19表達(dá)強(qiáng)烈區(qū)域瘤壁明顯變薄。表達(dá)部位定位于以棕黃色或棕褐色為特征的細(xì)胞核,在細(xì)胞漿的表達(dá)少見(jiàn)。對(duì)照組動(dòng)脈壁中膜平滑肌細(xì)胞的陽(yáng)性表達(dá)率為55.56%(25/45),主要表達(dá)于細(xì)胞漿。顱內(nèi)動(dòng)脈瘤瘤壁GRIM-19表達(dá)高于對(duì)照組中膜平滑肌細(xì)胞(P=0.00020.05),兩者相比差異有統(tǒng)計(jì)學(xué)意義。3.RT-PCR檢測(cè):在動(dòng)脈瘤組中在380bp處條帶亮度高于對(duì)照組。經(jīng)統(tǒng)計(jì)學(xué)處理,動(dòng)脈瘤組中膜平滑肌細(xì)胞GRIM-19m RNA的表達(dá)水平為O.96±O.10,對(duì)照組為O.63±0.11,t=8.42,P=0.00030.05,差異顯著有統(tǒng)計(jì)學(xué)意義,說(shuō)明動(dòng)脈瘤瘤壁中膜平滑肌細(xì)胞GRIM-19m RNA表達(dá)水平較正常顱內(nèi)小動(dòng)脈明顯增高。結(jié)論:1.顱內(nèi)動(dòng)脈瘤主要的組織病理學(xué)改變是瘤壁解剖結(jié)構(gòu)被破壞,血栓及動(dòng)脈粥樣硬化形成,炎性細(xì)胞侵潤(rùn),內(nèi)皮細(xì)胞及平滑肌細(xì)胞減少甚至消失,膠原纖維降解。2.GRIM-19在顱內(nèi)動(dòng)脈瘤瘤壁中膜平滑肌細(xì)胞中高表達(dá),而在對(duì)照組中相對(duì)低表達(dá),GRIM-19表達(dá)強(qiáng)烈區(qū)域瘤壁明顯變薄。推測(cè)GRIM-19可能通過(guò)凋亡途徑參與中膜平滑肌細(xì)胞減少的病理過(guò)程,進(jìn)而與顱內(nèi)動(dòng)脈瘤的形成和破裂相關(guān)。3.本研究從基因水平探究了顱內(nèi)動(dòng)脈瘤可能的發(fā)病機(jī)制,為其防治提供了新的實(shí)驗(yàn)依據(jù)。
[Abstract]:Objective: 1. to observe the histopathological changes of the aneurysm wall of human intracranial aneurysm; 2. to detect the expression of gene associated with retinoidinterferon-induced mortality-19 (GRIM-19) in the membrane smooth muscle cells of the aneurysm wall of intracranial aneurysm, and to explore the membrane level in the wall of intracranial aneurysm. The causes and possible mechanisms of smooth muscle cell reduction and its role in the occurrence and development of intracranial aneurysms. Methods: to collect and collate the cases of subarachnoid hemorrhage caused by intracranial aneurysms in the Department of Neurosurgery of the Affiliated Hospital of Sichuan Medical University in April January 2013 ~2014, and to select the intracranial aneurysm neck after craniotomy to close the intracranial aneurysm. 45 cases of pathological specimens obtained by resection of the tumor were classified as aneurysm group, including 16 males and 29 females. The control group was treated with craniocerebral trauma in the Department of Neurosurgery of the Affiliated Hospital of Sichuan Medical University for the same period. 45 cases of normal intracranial arterioles were collected by intracranial hematoma removal or internal decompression, including 27 males and 18 women. The two groups were all required. Before operation and patient safety, informed consent was signed before operation. The gross observation of two groups of specimens was observed by naked eye; the tissue structure of two groups of specimens was examined by light microscopy; RT-PCR technique and immunohistochemical SP method were used to detect the expression of GRIM-19 in the wall of intracranial aneurysm and the membrane smooth muscle cells in the normal vascular wall. The changes in the two cases were compared. All cases excluded hypertension, diabetes and other medical history. Results: 1. gross gross observation: the aneurysm body was mostly dark red, brown, cystic or fusiform appearance, mostly toughened, incision tumor, 12 specimens of the tumor wall visible white or dark red flattened, circular or oval atherosclerosis In 28 specimens, there was a thrombus in the cavity of the tumor. The thickness of the thrombus was softer. The thickness of the tumor wall gradually thinned from the neck of the tumor. The thinner top of the tumor was only the thin layer of fibrous membrane, even some had broken. All the ruptured aneurysms were observed at the top or near the top of the tumor. The blood vessels of the control group were bright red and the lumen had no obvious arterial atherosclerosis. .2. light microscopy of sclerotic plaque and wall attached thrombosis: HE staining: the thickness of the tube wall in the normal intracranial arteriole section is uniform, the internal, middle, and outer three layers of membrane anatomy are clear intact and intact, the cell morphology of each layer is normal, the myoselles of adjacent cells are closely connected, the middle layer smooth muscle cells are arranged in the concentric layer, and the wall inflammation cells are arranged. In the aneurysm group, the thickness of the wall of the tube was uneven, from the beginning of the tumor to the top of the tumor, the partial or whole layer of the wall of the tumor was expanded, the three layers of the membrane were dissected, the cells were partly or all destroyed, the inflammatory cells were infiltrated and diffused, the crystalline deposits of lipids and cholesterol were seen, and some of the wall of the tumor was visible. The positive expression rate of GRIM-19 in the membrane smooth muscle cells of 42 cases of intracranial aneurysm wall was 93.33% (42/45), and the strong region of GRIM-19 was obviously thinner. The expression site was located in the nuclei characterized by brown or brown brown. The positive expression rate of membrane smooth muscle cells in the arterial wall of the control group was 55.56% (25/45), which was mainly expressed in the cytoplasm. The expression of GRIM-19 in the aneurysm wall of intracranial aneurysms was higher than that of the control group of middle membrane smooth muscle cells (P=0.00020.05), and the difference was statistically significant.3.RT-PCR detection: in the aneurysm group, the band was in the 380bp band. The expression level of GRIM-19m RNA in the membrane smooth muscle cells in the aneurysm group was O.96 + O.10, and the control group was O.63 + 0.11, t=8.42, P=0.00030.05. The difference was statistically significant, indicating that the RNA expression level of the membrane smooth muscle cells in the aneurysm wall was significantly higher than that of the normal intracranial arteriole. 1. the major histopathological changes in intracranial aneurysms were the destruction of the anatomical structure of the tumor wall, thrombosis and atherosclerosis, inflammatory cells embellished, endothelial cells and smooth muscle cells reduced or even disappeared. The collagen fibrous degradation of.2.GRIM-19 was highly expressed in the membrane smooth muscle cells of the aneurysm wall of the intracranial aneurysm, but relatively low expression in the control group. It is suggested that GRIM-19 may be involved in the pathological process of the reduction of middle membrane smooth muscle cells through apoptotic pathway, which may be associated with the formation and rupture of intracranial aneurysms by.3.. The possible pathogenesis of intracranial aneurysms is explored from the gene level, which provides a new experimental basis for the prevention and treatment of GRIM-19.
【學(xué)位授予單位】：四川醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：R651.12

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