本文選題：肺動(dòng)脈高壓 + COPD　； 參考：《南華大學(xué)》2015年碩士論文

【摘要】：目的:研究COPD相關(guān)肺動(dòng)脈高壓(pulmonary hypertension,PH)患者肺血管重塑病理過程中,抵抗素樣分子β(resistin-like moleculeβ,RELMβ)及其介導(dǎo)的信號(hào)通路PI3K/Akt/m TOR在肺小動(dòng)脈血管壁的表達(dá)情況,明確上述蛋白在肺血管重塑過程中的作用。通過檢測COPD相關(guān)PH患者血漿中RELMβ、HIF-1a蛋白表達(dá)水平探討其與肺動(dòng)脈壓力的相關(guān)性,從而為研究COPD相關(guān)PH提供新的理論依據(jù)。方法:實(shí)驗(yàn)共分為兩個(gè)部分。第一部分收集因肺鱗癌行肺葉切除術(shù)患者的肺組織30例,通過血?dú)夥治觥⒎喂δ�、多普勒超聲心�?dòng)圖將其分為非COPD非PH組(對(duì)照組)、COPD非PH組(COPD組)、COPD相關(guān)PH組(PH組)。觀察各組肺血管重塑情況,免疫組織化學(xué)染色法(IHC)檢測RELMβ蛋白在肺組織的表達(dá)部位及水平,免疫蛋白印跡(Western blot,WB)檢測RELMβ、PI3K、Akt、m TOR蛋白在患者肺小動(dòng)脈血管壁上的表達(dá)情況,并探討上述蛋白在肺血管重塑過程中的作用。第二部分將因COPD急性加重而入院治療的80例患者通過血?dú)夥治�、肺功能、多普勒超聲心�?dòng)圖將其分為COPD相關(guān)PH組(PH組)、COPD非PH組(COPD組),并在體檢科隨機(jī)抽取行上述檢查的健康志愿者40例為對(duì)照組,采集各觀察組患者靜脈血5ml,通過離心機(jī)分離出血漿,用ELISA法檢測各組患者血漿中Relmβ、HIF-1a蛋白表達(dá)水平并探討其與肺動(dòng)脈壓力的相關(guān)性。結(jié)果:1、顯微鏡下觀察各組肺血管重塑(1)對(duì)照組顯微鏡下可見肺泡結(jié)構(gòu)清晰,肺泡間隔完整,肺小動(dòng)脈管壁較薄,血管腔未見狹窄。(2)COPD組較對(duì)照組相比,肺泡壁斷裂、融合,可見肺大泡形成,肺泡結(jié)構(gòu)破壞明顯,肺小動(dòng)脈血管壁增厚,血管腔狹窄明顯。COPD組肺小動(dòng)脈管壁厚度占外徑的百分比(WT%)、肺小動(dòng)脈管壁面積與血管總面積的比值(WA%)均高于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。而肺小動(dòng)脈管腔面積與管總面積的比值(LA%)低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。(3)PH組顯微鏡下可見肺大泡形成,其肺小動(dòng)脈血管中膜層顯著增厚,血管腔明顯狹窄,該組WT%、WA%、LA%較COPD組比較,差異均存在顯著統(tǒng)計(jì)學(xué)意義(P0.05)。2、免疫組織化學(xué)檢測各組肺小動(dòng)脈血管壁RELMβ表達(dá)免疫組織化學(xué)染色法結(jié)果顯示:COPD組與對(duì)照組相比,RELMβ表達(dá)明顯增強(qiáng),差異具有統(tǒng)計(jì)學(xué)意義(P0.05);PH組則呈強(qiáng)陽性表達(dá),與COPD組比較差異有統(tǒng)計(jì)學(xué)意義(P0.05)。3、Western blot檢測各組患者肺組織內(nèi)RELMβ、PI3K/Akt/m TOR信號(hào)通路蛋白表達(dá)Western blot結(jié)果顯示:Relmβ在COPD組表達(dá)量顯著高于對(duì)照組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05);PH組Relmβ蛋白表達(dá)量高于COPD組,結(jié)果有統(tǒng)計(jì)學(xué)意義(P0.05);p-PI3K在COPD組表達(dá)量顯著高于對(duì)照組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05);p-PI3K在PH組表達(dá)量顯著高于COPD組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05);p-Akt308在COPD組表達(dá)量明顯高于對(duì)照組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05);Akt308在PH組表達(dá)量明顯高于COPD組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05);p-Akt473在COPD組表達(dá)量明顯高于對(duì)照組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05);p-Akt473在PH組表達(dá)量明顯高于COPD組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05);p-m TOR在COPD組表達(dá)量明顯高于對(duì)照組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05);p-m TOR在PH組表達(dá)量明顯高于COPD組,結(jié)果具有統(tǒng)計(jì)學(xué)意義(P0.05)。直線相關(guān)分析顯示,患者肺組織內(nèi)Relmβ蛋白與WT%、WA%、PASP呈正相關(guān),與LA%、動(dòng)脈血氧分壓(Pa O2)呈負(fù)相關(guān)。4、ELISA檢測各組患者血漿中Relmβ、HIF-1a表達(dá)COPD組患者血漿中Relmβ表達(dá)量與對(duì)照組相比,差異具有統(tǒng)計(jì)學(xué)意義(P0.05);PH組患者血漿中Relmβ表達(dá)量與COPD組相比,具有顯著統(tǒng)計(jì)學(xué)差異(P0.05);COPD組患者血漿中HIF-1a表達(dá)量與對(duì)照組相比,差異具有統(tǒng)計(jì)學(xué)意義(P0.05);COPD組患者血漿中HIF-1a表達(dá)量與PH組相比,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。直線相關(guān)分析顯示,患者血漿中RELMβ蛋白表達(dá)與PASP、HIF-1a呈正相關(guān),與Pa O2呈負(fù)相關(guān),而患者血漿中HIF-1a蛋白表達(dá)與PASP呈正相關(guān),與Pa O2呈負(fù)相關(guān)。1、COPD相關(guān)PH患者肺小動(dòng)脈血管壁中Relmβ表達(dá)顯著增高,并可能通過激活PI3K/Akt/m TOR信號(hào)通路,參與肺血管重塑,從而導(dǎo)致PH的形成。2、COPD相關(guān)PH患者血漿中Relmβ、HIF-1a表達(dá)顯著增高,并與肺動(dòng)脈壓力呈正相關(guān)。結(jié)論:
[Abstract]:Objective: To investigate the expression of resistin-like molecule beta (RELM beta) and its mediated signaling pathway PI3K/Akt/m TOR in the vascular wall of pulmonary artery in the pathological process of pulmonary vascular remodeling in patients with COPD associated pulmonary hypertension (PH), and to clarify the role of these proteins in the process of pulmonary vascular remodeling. The correlation between RELM beta and HIF-1a protein expression in the plasma of COPD related PH patients was examined to provide a new theoretical basis for the study of COPD related PH. Methods: the experiment was divided into two parts. The first part collected 30 cases of lung tissue from patients with lung squamous cell carcinoma with pulmonary lobectomy, through blood gas analysis, lung function, and multip It was divided into non COPD non PH group (control group), non PH group COPD (group COPD), COPD related PH group (PH group). The pulmonary vascular remodeling was observed in each group. Immunohistochemistry staining method (IHC) was used to detect the expression of RELM beta protein in the lung tissue. The expression of the expression on the vascular wall of the pulmonary artery and the role of the above protein in the process of pulmonary vascular remodeling. Second part of the 80 patients who were hospitalized for the acute exacerbation of COPD were divided into COPD related PH group (group PH), COPD non PH group (group COPD), and random extraction in the physical examination department. 40 healthy volunteers were taken as the control group. The venous blood 5ml was collected from the observation groups and the blood plasma was separated by centrifuge. The level of Relm beta, HIF-1a protein expression in the plasma of each group was detected by ELISA and the correlation between the pulmonary pressure and the pulmonary artery pressure was investigated. Results: 1, the pulmonary vascular remodeling (1) in each group was observed under microscope (1). Microscopically, the alveolar structure was clear, the alveolar septum was complete, the wall of the pulmonary arteriole was thinner and the vascular cavity was not narrow. (2) compared with the control group, the alveolar wall was broken, the pulmonary bullae formed, the alveolar structure was damaged obviously, the pulmonary artery wall was thickened, the stenosis of the vascular cavity was obvious in the.COPD group, and the thickness of the tube wall of the pulmonary artery accounted for 100 percent of the diameter in the COPD group. The ratio of pulmonary arteriole wall area to total vascular area (WA%) was higher than that of the control group (WT%), and the difference was statistically significant (P0.05). The ratio of the lumen area to the total area of the pulmonary artery was lower than that of the control group (LA%), the difference was statistically significant (P0.05). (3) the formation of the pulmonary bullae was observed under the microscope of the group PH, and the membrane of the pulmonary arteriole was significant. Thickening, the vascular cavity was obviously narrowed, the group WT%, WA%, LA% compared with the COPD group, the difference was statistically significant (P0.05).2. The immunohistochemical staining of the RELM beta expression of the vascular wall of the pulmonary arterioles in each group showed that the RELM beta expression was obviously enhanced in COPD group compared with the control group, and the difference was statistically significant (P0.05); P H group showed strong positive expression, compared with group COPD (P0.05).3, Western blot detected RELM beta in the lung tissue of the patients, PI3K/Akt/m TOR signaling pathway protein expression Western blot results showed that the expression of Relm beta in the group was significantly higher than that of the control group, and the result was statistically significant. In group COPD, the results were statistically significant (P0.05); the expression of p-PI3K in group COPD was significantly higher than that in the control group (P0.05); the expression of p-PI3K in the PH group was significantly higher than that in the group COPD (P0.05), and the expression of p-Akt308 in the COPD group was significantly higher than that in the control group, and the results were statistically significant (P0.05). The expression of the group was significantly higher than that of the COPD group (P0.05), and the expression of p-Akt473 in the group COPD was significantly higher than that in the control group (P0.05), and the expression of p-Akt473 in the PH group was significantly higher than that of the COPD group, and the results were statistically significant (P0.05); P-M TOR in the COPD group was significantly higher than that of the control group, and the results were statistically significant. The expression of P-M TOR in the PH group was significantly higher than that in the COPD group, and the results were statistically significant (P0.05). The linear correlation analysis showed that the Relm beta protein in the lung tissue was positively correlated with WT%, WA%, PASP, and was negatively correlated with LA%, arterial oxygen pressure (Pa). The expression of Relm beta was statistically significant compared with that of the control group (P0.05). The plasma Relm beta expression in the PH group was significantly different from that in the COPD group (P0.05). The plasma HIF-1a expression in the COPD group was statistically significant compared with the control group (P0.05), and the HIF-1a expression in the plasma of the COPD group was compared with the PH group. The difference was statistically significant (P0.05). The linear correlation analysis showed that the expression of RELM beta protein in plasma was positively correlated with PASP, HIF-1a, and negatively correlated with Pa O2, but the expression of HIF-1a protein in the plasma was positively correlated with PASP, and negative correlation with Pa O2. The PI3K/Akt/m TOR signaling pathway is activated to participate in pulmonary vascular remodeling, resulting in the formation of PH.2. The expression of Relm beta and HIF-1a in the plasma of COPD related PH patients is significantly higher, and is positively correlated with the pulmonary arterial pressure.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R544.1

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