GRIM-19在人颅内动脉瘤壁中膜平滑肌细胞中的表达变化及其意义

发布时间：2018-06-09 05:51

本文选题：颅内动脉瘤 + 发病机制　；参考：《四川医科大学》2015年硕士论文

【摘要】：目的:1.观察人颅内动脉瘤瘤壁的组织病理学改变;2.检测干扰素/维甲酸联合诱导细胞凋亡相关基因19(gene associated with retinoidinterferon-induced mortality-19,GRIM-19)在颅内动脉瘤瘤壁中膜平滑肌细胞中的表达情况,探讨颅内动脉瘤瘤壁中膜平滑肌细胞减少的原因及可能机制及其在颅内动脉瘤发生、发展中的作用。方法:收集整理四川医科大学附属医院神经外科于2013年1月~2014年4月收治的颅内动脉瘤所致蛛网膜下腔出血的病例,选择经开颅显微手术夹闭颅内动脉瘤瘤颈后切除瘤囊获得的45例病理标本,并将其归为动脉瘤组,其中男16例,女29例。对照组为四川医科大学附属医院神经外科同期收治的颅脑外伤患者,经颅内血肿清除术或内减压术收集的45例正常颅内小动脉,其中男27例,女18例。两组标本均要求在保证手术及患者安全的情况下获得,手术前签知情同意书。对两组标本分别进行肉眼大体观察;制备切片行光镜检查两组标本组织结构;RT-PCR技术、免疫组化SP法检测GRIM-19在颅内动脉瘤瘤壁及正常血管壁中膜平滑肌细胞中的表达情况,比较二者的变化。所有病例排除高血压、糖尿病等病史者。结果:1.肉眼大体观察:动脉瘤组标本瘤体大多呈暗红色、棕褐色,囊状或梭形外观,大多质韧,切开瘤体,12例标本瘤壁可见表面白色或暗红色的扁平状、圆形或椭圆形动脉粥样硬化斑块,28例标本瘤腔内有附壁血栓,血栓质地较软。其瘤壁厚度从瘤颈开始逐渐变薄,瘤顶最薄者仅残存薄层纤维膜,甚至有的已经破裂。观察见所有破裂动脉瘤,破口均在瘤顶或近瘤顶处。对照组标本血管呈鲜红色,管腔未见明显动脉粥样硬化斑块及附壁血栓。2.光镜观察:HE染色:正常颅内小动脉切片光镜下见管壁厚薄均匀,内、中、外三层膜解剖结构清晰完整无破坏,各层细胞形态正常,相邻细胞的肌膜常都形成紧密连接,中层平滑肌细胞呈同心层结构排列,管壁炎性细胞少见。动脉瘤组切片光镜下见管壁厚薄不均,从瘤颈开始到瘤顶逐渐变薄,部分瘤壁局部或全层向外膨出,三层膜解剖结构不清,瘤壁内细胞部分或全部破坏,炎性细胞浸润且分部弥漫,可见脂类物质及胆固醇结晶沉积,部分瘤壁可见机化的血栓或粘附于囊内壁的新鲜血栓,中层平滑肌细胞减少。免疫组化染色:GRIM-19在42例颅内动脉瘤瘤壁中膜平滑肌细胞中的阳性表达率为93.33%(42/45),GRIM-19表达强烈区域瘤壁明显变薄。表达部位定位于以棕黄色或棕褐色为特征的细胞核,在细胞浆的表达少见。对照组动脉壁中膜平滑肌细胞的阳性表达率为55.56%(25/45),主要表达于细胞浆。颅内动脉瘤瘤壁GRIM-19表达高于对照组中膜平滑肌细胞(P=0.00020.05),两者相比差异有统计学意义。3.RT-PCR检测:在动脉瘤组中在380bp处条带亮度高于对照组。经统计学处理,动脉瘤组中膜平滑肌细胞GRIM-19m RNA的表达水平为O.96±O.10,对照组为O.63±0.11,t=8.42,P=0.00030.05,差异显著有统计学意义,说明动脉瘤瘤壁中膜平滑肌细胞GRIM-19m RNA表达水平较正常颅内小动脉明显增高。结论:1.颅内动脉瘤主要的组织病理学改变是瘤壁解剖结构被破坏,血栓及动脉粥样硬化形成,炎性细胞侵润,内皮细胞及平滑肌细胞减少甚至消失,胶原纤维降解。2.GRIM-19在颅内动脉瘤瘤壁中膜平滑肌细胞中高表达,而在对照组中相对低表达,GRIM-19表达强烈区域瘤壁明显变薄。推测GRIM-19可能通过凋亡途径参与中膜平滑肌细胞减少的病理过程,进而与颅内动脉瘤的形成和破裂相关。3.本研究从基因水平探究了颅内动脉瘤可能的发病机制,为其防治提供了新的实验依据。
[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.
【学位授予单位】：四川医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R651.12

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