【摘要】：背景:動脈粥樣硬化(Atherosclerosis,AS)發病率逐年升高,而由此引發的冠心病及近年來日益受到關注的急性冠脈綜合征(Acute Coronary Syndromes,ACS)亦對健康造成威脅,嚴重者直接危害生命。隨著相關研究的深入及擴展,整合素α5β1(Integrinα5β1)及其下游關鍵通路黏著斑激酶(Focal Adhesion Kinase,FAK)逐漸被納入視線。最初研究表明FAK與與人類許多惡性腫瘤的發生、侵襲、轉移及預后有著密切聯系,如結腸、乳腺癌、胃癌、非小細胞肺癌等。FAK的生物學效應主要依賴于關鍵位點(Tyr397)的磷酸化而實現。另有文獻報道,FAK在胚胎期血管生成及血管損傷后血管新生等修復過程中發揮重要作用,并且參與內皮細胞、平滑肌細胞的遷移及增殖等生物學過程。故推測其參與并促進動脈粥樣硬化發生、發展。目的:本實驗通過免疫組織化學的方法,檢測FAK、Phospho FAK、CD131、CD68、actin在實驗組(動脈粥樣硬化組)、對照組(正常動脈組)中表達的情況。綜合分析粥樣硬化斑塊FAK、Phospho FAK的表達情況與二者的相關性,及二者與AS發生、發展的關系。方法:標本選自近5年大連醫科大學病理學與法醫學教研室尸檢標本100例。分別取左冠脈前降支、左旋支及右冠脈。主要實驗手段采用免疫組織化學方法、彈力纖維染色法,并應用圖像分析軟件對圖像進行分析及處理。以CD68與actin的表達定位FAK、Phospho FAK的表達情況。CD131標記新生血管,并計數新生血管的密度來檢測FAK與血管新生的相關性。彈力纖維染色及NIH Scion Image(60.1)軟件的應用判定冠狀動脈狹窄程度。依據粥樣硬化斑塊的不同時期分為脂紋組及粥樣硬化斑塊組;依據EVG染色及軟件分析結果,按狹窄程度將實驗組冠脈分為4個亞組:分別為A組(≤25%)、B組(25%-50%)、C組(51%-75%)、D組(≥76%);依據病史及是否有急性心梗發作將病例分為ACS組、陳舊心梗組及正常組。結果:1)FAK與Phospho FAK均表達于內皮細胞胞漿,內膜間質細胞胞漿,巨噬細胞胞漿,平滑肌細胞胞漿,尤以遷移至內膜的平滑肌細胞表達高及鈣化灶處。2)FAK在平滑肌細胞的表達強度與狹窄程度的關系:隨著狹窄程度的升高而降低,兩兩比較分析P值均為0.000。Phospho FAK在平滑肌細胞的表達強度與狹窄程度關系呈現隨狹窄程度升高而降低趨勢,P值分別為:A組與B組0.011,A組與C組0.172,A組與D組0.000,B組與C組0.221,B組與D組0.000,C組與D組0.000。3)FAK與Phospho FAK的表達與斑塊局部血管新生的關系局部血管新生的數量隨二者的表達強度增加而增多,FAK與Phospho FAK與新生血管之間存在一定的正相關性,且具有統計學意義(RFAK=0.983,PFAK=0.000;RPhospho FAK=0.994,PPh FAK=0.000)。4)FAK與Phospho FAK在動脈粥樣硬化斑塊組平滑肌細胞的表達呈明顯正相關性(R=0.904,P=0.000)。此外,FAK與Phospho FAK在非斑塊底部平滑肌胞漿的表達高于斑塊底部平滑肌,且FAK與Phospho FAK在內膜近內彈力板處間質的表達脂紋期高于粥樣硬化斑塊期。結論:1.FAK與Phospho FAK通過激活內皮細胞、促進平滑肌細胞遷移、誘導斑塊局部血管新生等途徑參與冠狀動脈粥樣硬化的發生、發展。2.FAK與Phospho FAK參與動脈粥樣硬化局部鈣化的發生。
[Abstract]:BACKGROUND: The incidence of atherosclerosis (AS) is increasing year by year. Coronary heart disease (CHD) and acute coronary syndrome (ACS), which have attracted more and more attention in recent years, also pose a threat to health and directly endanger life. With the deepening and expansion of relevant studies, integrin alpha 5 beta 1 (Integrin alpha 5 beta 1) Focal Adhesion Kinase (FAK), a key downstream pathway of FAK, has been gradually brought into view. Initial studies have shown that FAK is closely related to the occurrence, invasion, metastasis and prognosis of many human malignancies, such as colon, breast cancer, gastric cancer, non-small cell lung cancer, etc. The biological effects of FAK mainly depend on the key site (Tyr397). In addition, FAK has been reported to play an important role in the process of angiogenesis and angiogenesis after vascular injury in embryonic period. It is also involved in the migration and proliferation of endothelial cells and smooth muscle cells. Methods: The expression of FAK, Phospho FAK, CD131, CD68 and actin in experimental group (atherosclerosis group) and control group (normal artery group) were detected by histochemical method. The left anterior descending coronary artery, left circumflex coronary artery and right coronary artery were taken respectively. Immunohistochemistry, elastic fiber staining and image analysis software were used to analyze and process the images. Elastic fiber staining and NIH Scion Image (60.1) software were used to determine the degree of coronary artery stenosis. The coronary arteries of the experimental group were divided into four subgroups according to the degree of narrowness: group A (< 25%), group B (25% - 50%), group C (51% - 75%) and group D (> 76%). The patients were divided into ACS group, old myocardial infarction group and normal group according to the history and whether there was acute myocardial infarction attack. The expression of FAK in smooth muscle cells decreased with the increase of stenosis, and the P value was 0.000. The relationship between the expression of Phospho FAK in smooth muscle cells and the degree of stenosis was narrow. The expression of FAK and Phospho FAK and local angiogenesis of plaque increased with the increase of expression intensity of FAK and Phospho FAK, and the number of local angiogenesis of plaque increased with the increase of expression intensity of FAK and Phospho FAK and Phospho FAK. There was a positive correlation between FAK and Phospho FAK in atherosclerotic plaque (R = 0.904, P = 0.000). In addition, FAK and Phospho FAK were positively correlated in non-plaque basal smooth muscle cytoplasm. The expression of FAK and Phospho FAK in the stroma near the intimal elastic plate was higher than that in atherosclerotic plaque. Conclusion: 1. FAK and Phospho FAK participate in the pathogenesis and development of coronary atherosclerosis by activating endothelial cells, promoting the migration of smooth muscle cells and inducing local angiogenesis of plaque. .FAK and Phospho FAK participate in the occurrence of atherosclerotic local calcification.
【學位授予單位】：大連醫科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R541.4

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