FAK及磷酸化FAK在尸檢標本中冠狀動脈粥樣硬化局部的表達及意義
發(fā)布時間：2018-08-20 17:44
【摘要】：背景:動脈粥樣硬化(Atherosclerosis,AS)發(fā)病率逐年升高,而由此引發(fā)的冠心病及近年來日益受到關(guān)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(guān)研究的深入及擴展,整合素α5β1(Integrinα5β1)及其下游關(guān)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(fā)生、侵襲、轉(zhuǎn)移及預后有著密切聯(lián)系,如結(jié)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(guān)鍵位點(Tyr397)的磷酸化而實現(xiàn)。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(fā)揮重要作用,并且參與內(nèi)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(fā)生、發(fā)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(guān)性,及二者與AS發(fā)生、發(fā)展的關(guān)系。方法:標本選自近5年大連醫(yī)科大學病理學與法醫(yī)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(shù)新生血管的密度來檢測FAK與血管新生的相關(guān)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(jù)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(jù)EVG染色及軟件分析結(jié)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(jù)病史及是否有急性心梗發(fā)作將病例分為ACS組、陳舊心梗組及正常組。結(jié)果:1)FAK與Phospho FAK均表達于內(nèi)皮細胞胞漿,內(nèi)膜間質(zhì)細胞胞漿,巨噬細胞胞漿,平滑肌細胞胞漿,尤以遷移至內(nèi)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(guān)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(guān)系呈現(xiàn)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(guān)系局部血管新生的數(shù)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(guān)性,且具有統(tǒng)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(guān)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(nèi)膜近內(nèi)彈力板處間質(zhì)的表達脂紋期高于粥樣硬化斑塊期。結(jié)論:1.FAK與Phospho FAK通過激活內(nèi)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(fā)生、發(fā)展。2.FAK與Phospho FAK參與動脈粥樣硬化局部鈣化的發(fā)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(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R541.4
本文編號：2194478
[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(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R541.4
【參考文獻】
相關(guān)期刊論文 前3條
1 姚睿原;賈曉陽;郝慧芳;;FAK/mTOR信號通路在腫瘤細胞中的調(diào)控作用[J];中國生物化學與分子生物學報;2016年01期
2 楊慧;林春龍;;FAK在COPD呼吸道平滑肌細胞增殖中作用機制的研究進展[J];醫(yī)學綜述;2014年22期
3 高敏;劉肖珩;孫亨;任弘毅;王利娟;沈陽;;FAK通過粘著斑蛋白調(diào)控血管內(nèi)皮細胞遷移的研究[J];生物醫(yī)學工程學雜志;2013年03期
相關(guān)博士學位論文 前1條
1 劉智敏;整合素β_3-FAK信號途徑活化與血管平滑肌細胞遷移的關(guān)系及作用機制[D];河北醫(yī)科大學;2003年
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