本文選題：慢性支氣管炎 + 冠狀動(dòng)脈粥樣硬化　； 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：第一部分機(jī)體慢性炎癥與冠狀動(dòng)脈粥樣硬化的相關(guān)性分析目的:從病理學(xué)角度探討慢性炎癥與冠狀動(dòng)脈粥樣硬化(coronary atherosclerosis,CAS)的相關(guān)性。方法:回顧性分析涉及慢性炎癥和(或)CAS患者的病歷及尸體檢驗(yàn)資料。結(jié)果:CAS合并一種及以上慢性炎癥216例,其中男性159例(73.61%),女性57例(26.39%);左冠狀動(dòng)脈前降支最易發(fā)生粥樣硬化及狹窄;CAS患者中慢性支氣管炎(chronic bronchitis,CB)196例,CB與CAS呈正相關(guān)(rs=0.404,P=0.000),且是CAS發(fā)生的危險(xiǎn)因素之一(OR=4.852,95%CI=2.898~8.124,P=0.000),其他慢性炎癥如慢性腎盂腎炎、慢性胃腸炎、慢性食管炎、慢性淋巴細(xì)胞甲狀腺炎及慢性宮頸炎與CAS均無明顯相關(guān)性(P0.05)。結(jié)論:CB是CAS發(fā)生發(fā)展的危險(xiǎn)因素之一;臨床上應(yīng)重視CB的治療,從而降低冠心病的發(fā)生率和死亡率。第二部分炎癥因子與骨相關(guān)蛋白表達(dá)及CAS斑塊鈣化的相關(guān)性研究目的:檢測(cè)CAS斑塊中鈣鹽相對(duì)含量,并檢測(cè)斑塊中白細(xì)胞介素-6(interleukin-6,IL-6)和骨相關(guān)蛋白,如骨鈣蛋白(bone gla protein,BGP)、骨橋蛋白(osteopontin,OPN)及Runt相關(guān)轉(zhuǎn)錄因子2(runt-related transcription factor 2,RUNX2)的表達(dá)情況,探討成骨表型細(xì)胞的來源、IL-6與骨相關(guān)蛋白表達(dá)及CAS斑塊鈣化的相關(guān)性。方法:以人體CAS斑塊為研究對(duì)象,根據(jù)管腔狹窄程度將實(shí)驗(yàn)分為五組:正常組、I級(jí)狹窄組、II級(jí)狹窄組、III級(jí)狹窄組及IV級(jí)狹窄組。通過HE染色及特殊染色觀察各組斑塊的形態(tài)學(xué)改變,并分析鈣鹽相對(duì)含量;免疫組化檢測(cè)成骨表型細(xì)胞的來源;免疫組化及Western Blot實(shí)驗(yàn)檢測(cè)斑塊中骨相關(guān)蛋白表達(dá),并對(duì)IL-6與骨相關(guān)蛋白表達(dá)的相關(guān)性進(jìn)行分析。結(jié)果:冠狀動(dòng)脈鈣化率隨管腔狹窄程度的增加而增加,II-IV級(jí)狹窄組可見不同程度鈣鹽沉積,且II-IV級(jí)狹窄組中鈣鹽相對(duì)含量差異有統(tǒng)計(jì)學(xué)意義(P0.05)。早期CAS斑塊(I-II級(jí)狹窄組)成骨表型細(xì)胞主要來源于單核-巨噬細(xì)胞,而中晚期CAS斑塊(III-IV級(jí)狹窄組)成骨表型細(xì)胞主要來源于血管平滑肌細(xì)胞(vascular smooth muscle cells,VSMCs)。IL-6、BGP、OPN及RUNX2表達(dá)隨管腔狹窄程度的增加而增強(qiáng),IL-6、BGP及RUNX2在I-IV級(jí)狹窄組均較正常組表達(dá)有統(tǒng)計(jì)學(xué)意義(P0.01),而OPN在II-IV級(jí)狹窄組均較正常組表達(dá)有統(tǒng)計(jì)學(xué)意義(P0.01)。蛋白激酶A(Protein kinase A,PKA)及環(huán)腺苷酸-反應(yīng)元件結(jié)合蛋白(Cyclic adenosine monophosphate-response element binding protein,CREB)在II-IV級(jí)狹窄組較正常組表達(dá)有統(tǒng)計(jì)學(xué)意義(P0.01)。IL-6與骨相關(guān)蛋白(BGP、OPN及RUNX2)表達(dá)量均存在線性正相關(guān)(r值分別為0.790、0.986、0.919,P0.01)。結(jié)論:冠狀動(dòng)脈VSMCs在炎癥因子介導(dǎo)c AMP-PKA通路作用下向成骨細(xì)胞表型轉(zhuǎn)變及表達(dá)骨相關(guān)蛋白最終導(dǎo)致CAS斑塊中鈣鹽沉積。
[Abstract]:Analysis of the correlation between chronic inflammation and coronary atherosclerosis in part 1 Objective: To investigate the correlation between chronic inflammation and coronary atherosclerosis (CAS) from a pathological point of view. Methods: a retrospective analysis of the records of patients with chronic inflammation and / or CAS and the data of cadavers. Results: CAS combined with one kind. There were 216 cases of chronic inflammation, including 159 males (73.61%) and 57 females (26.39%). Left anterior descending coronary artery was the most susceptible to atherosclerosis and stenosis, and 196 cases of chronic bronchitis (chronic bronchitis, CB) in CAS patients, CB and CAS (rs=0.404, P= 0), and one of the risk factors for CAS (OR=4.852,95%CI=2.898~8.124, P=0) .000), other chronic inflammation such as chronic pyelonephritis, chronic gastroenteritis, chronic esophagitis, chronic lymphocytic thyroiditis and chronic cervicitis have no significant correlation with CAS (P0.05). Conclusion: CB is one of the risk factors for the development of CAS; the treatment of CB should be paid attention to in clinical, so as to reduce the incidence and mortality of coronary heart disease. Second parts The correlation between inflammatory factors and bone related protein expression and CAS plaque calcification Objective: to detect the relative calcium salt content in CAS plaque, and to detect interleukin -6 (interleukin-6, IL-6) and bone associated protein in plaque, such as bone gla protein (BGP), bone bridge protein (osteopontin, OPN), and Runt related transcription factor 2 Anscription factor 2, RUNX2) expression, the origin of osteoblast phenotype cells, the correlation between IL-6 and bone related protein expression and CAS plaque calcification. Methods: the human CAS plaque as the research object, according to the degree of stenosis of the lumen, the experiment is divided into five groups: normal group, I stricture group, II stricture group, III stricture group and IV stricture group. The morphological changes of plaque in each group were observed by HE staining and special staining, and the relative content of calcium salt was analyzed; the source of osteoblast phenotype was detected by immunohistochemistry; the expression of bone related protein in plaque was detected by immunohistochemistry and Western Blot, and the correlation between the expression of IL-6 and bone related protein was analyzed. The increase in the degree of stenosis of the lumen increased. The II-IV stenosis group showed different degrees of calcium salt deposition, and there was a significant difference in the relative calcium salt content in the II-IV stenosis group (P0.05). The early CAS plaque (I-II class stenosis group) was mainly derived from the mononuclear macrophage, while the middle and late CAS plaque (III-IV stricture) was the osteoblast phenotype. The cells were mainly derived from vascular smooth muscle cells (vascular smooth muscle cells, VSMCs).IL-6, and the expression of BGP, OPN and RUNX2 increased with the increase of the stenosis of the lumen. IL-6, BGP and RUNX2 in the stricture group were all more significant than those in the normal group. The expression of protein kinase A (Protein kinase A, PKA) and cyclic adenylate reaction element binding protein (Cyclic adenosine monophosphate-response element binding protein, CREB) had a statistically significant linear correlation with the expression of bone associated protein (0.7). 90,0.986,0.919, P0.01) conclusion: the transformation of the osteoblast to the osteoblast and the expression of bone related protein in the coronary artery VSMCs under the action of the inflammatory factor mediated C AMP-PKA pathway eventually lead to calcium salt deposition in the CAS plaque.

【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：D919

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1 聶倩云;炎癥因子介導(dǎo)cAMP-PKA通路作用下VSMCs表達(dá)骨相關(guān)蛋白與CAS斑塊鈣化的相關(guān)性研究[D];重慶醫(yī)科大學(xué);2017年

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