【摘要】：目的:慢性肺源性心臟病,簡稱慢性肺心病,是一種常見的呼吸系統(tǒng)慢性疾病。患者肺、心功能均受到不同程度的損害,病情逐漸進(jìn)展,對患者的生活質(zhì)量及生存壽命造成嚴(yán)重影響。目前,慢性肺心病的發(fā)病機(jī)制尚未完全明確,但得到廣泛認(rèn)同的是,低氧性肺動脈高壓是其發(fā)生、發(fā)展的中心環(huán)節(jié)。低氧性肺動脈高壓包含兩方面重要的病理生理學(xué)改變,即低氧性肺血管收縮和低氧性肺血管重構(gòu),后者使肺動脈的解剖結(jié)構(gòu)發(fā)生變化,形成肺循環(huán)血流動力學(xué)的障礙。低氧性肺血管重構(gòu)是肺動脈高壓由可逆性轉(zhuǎn)變?yōu)槌掷m(xù)存在的決定因素,也是臨床上血管舒張藥物治療肺動脈高壓需要攻克的難點(diǎn)。轉(zhuǎn)化生長因子b1(transforming growth factorβ1,TGF-β1)是新近發(fā)現(xiàn)的一種調(diào)節(jié)細(xì)胞生長和分化的細(xì)胞因子,在促纖維化及組織結(jié)構(gòu)重構(gòu)方面作用顯著,可以引起血管壁實(shí)質(zhì)細(xì)胞的增殖、肥大、重排、遷移、凋亡和細(xì)胞外基質(zhì)增加�，F(xiàn)有研究表明TGF-β1的蛋白、m RNA在低氧誘導(dǎo)的慢性肺心病動物模型的支氣管粘膜、肺組織、肺血管管壁及支氣管肺泡灌洗液、血清中均處于高表達(dá),提示低氧可能導(dǎo)致TGF-β1表達(dá)水平增加,活化的TGF-β1在推動肺動脈高壓及肺心病的形成和發(fā)展過程中扮演著重要角色,由此推測TGF-β1水平在慢性肺心病患者血清中也可能是升高的。本研究測定了90例慢性肺心病患者在不同時期下(急性加重期和緩解期)血清TGF-β1的表達(dá)水平,并將其與動脈血氧分壓(Pa O2)及反映肺動脈高壓、右心室擴(kuò)大的超聲指標(biāo)—主肺動脈內(nèi)徑(MPAD)、右室內(nèi)徑(RVD)、肺動脈收縮壓(PASP)進(jìn)行相關(guān)性分析,進(jìn)一步探究TGF-β1在慢性肺源性心臟病中的作用,為其防治提供新的臨床思路。方法:慢性肺心病急性加重期患者90例,男62例,女28例,年齡58~83歲,平均(69.77±7.24)歲,經(jīng)常規(guī)治療癥狀、體征等病情穩(wěn)定后2周作為緩解期組。選取性別、年齡等一般資料相匹配的90例健康人為健康對照組。各組血清TGF-β1的測定采用酶聯(lián)免疫吸附法(ELISA),并應(yīng)用SPSS19.0統(tǒng)計軟件進(jìn)行one-way ANOVA。患者急性加重期和緩解期均行彩色超聲心動圖檢查,測量MPAD、RVD、PASP參數(shù)指標(biāo),并行動脈血?dú)夥治鰷y定Pa O2,上述檢測指標(biāo)均與血清TGF-β1水平行相關(guān)分析。結(jié)果:1.一般資料慢性肺心病急性加重期患者90例,其中男62例,女28例,平均年齡(69.77±7.24)歲,彩色超聲心動圖測得的平均主肺動脈內(nèi)徑(MPAD)為(25.97±3.37)mm,平均右室內(nèi)徑為(26.43±2.99)mm,平均肺動脈收縮壓(PASP)為(54.41±6.85)mm Hg。急性加重期患者經(jīng)常規(guī)治療病情緩解后測得的平均主肺動脈內(nèi)徑(MPAD)為(25.07±3.38)mm,平均右室內(nèi)徑為(26.45±3.67)mm,平均肺動脈收縮壓(PASP)為(49.36±6.86)mm Hg。健康對照組90例,其中男60例,女30例,平均年齡(68.90±5.79)歲,平均主肺動脈內(nèi)徑(MPAD)為(19.13±2.84)mm,平均右室內(nèi)徑為(20.31±4.11)mm。2.各組血清TGF-β1水平TGF-β1在慢性肺心病患者急性加重期、緩解期及健康對照組受試者血清中的表達(dá)水平分別為(306.12±27.04)pg/ml、(161.16±24.00)pg/ml、(82.15±24.34)pg/ml。三組間血清TGF-β1水平差異均有統(tǒng)計學(xué)意義(P0.05)。3.慢性肺心病患者血清TGF-β1水平與Pa O2的相關(guān)性慢性肺心病患者急性加重期和緩解期血清TGF-β1水平均與Pa O2呈負(fù)相關(guān)(r=-0.739,P0.05;r=-0.619,P0.05)。且急性加重期Pa O2水平明顯低于緩解期,差異有統(tǒng)計學(xué)意義(P0.05)。4.慢性肺心病患者血清TGF-β1水平與心臟超聲右心參數(shù)MPAD、RVD、PASP的相關(guān)性慢性肺心病患者急性加重期血清TGF-β1水平與MPAD、RVD、PASP均呈正相關(guān)(r=0.740,P0.05;r=0.792,P0.05;r=0.878,P0.05);緩解期血清TGF-β1水平也與MPAD、RVD、PASP均呈正相關(guān)(r=0.600,P0.05;r=0.718,P0.05;r=0.630,P0.05)。結(jié)論:1.慢性肺心病患者血清TGF-β1水平明顯高于健康對照組,且與反應(yīng)肺動脈高壓、右心室擴(kuò)大的超聲指標(biāo)呈正相關(guān),表明TGF-β1極有可能參與了慢性肺心病的病理生理過程。2.慢性肺心病患者血清TGF-β1水平與Pa O2呈負(fù)相關(guān),表明TGF-β1水平升高可能與缺氧刺激有關(guān)。3.慢性肺心病患者急性加重期血清TGF-β1水平顯著高于緩解期,提示TGF-β1水平監(jiān)測可為慢性肺心病患者病情評估、觀察療效提供一種新的可能手段。4.慢性肺心病患者血清TGF-β1水平升高與低氧和右心系統(tǒng)病變關(guān)系密切,拮抗TGF-β1信號傳導(dǎo)途徑或抑制其活性有可能為慢性肺心病的防治提供新的思路。
[Abstract]:Objective: chronic pulmonary heart disease (CCHD), referred to as chronic cor pulmonale, is a common chronic respiratory disease. The lung and heart function of the patients are impaired in varying degrees, and the disease progresses gradually. The quality of life and life life of the patients is seriously affected. Hypoxic pulmonary hypertension is the central part of its development. Hypoxic pulmonary hypertension contains two important pathophysiological changes, namely hypoxic pulmonary vasoconstriction and hypoxic pulmonary vascular remodeling. The latter causes changes in the anatomical structure of the pulmonary artery, the obstacle of pulmonary circulation hemodynamics, and hypoxic pulmonary vessels. Remodeling is the determinant of the reversible transformation of pulmonary artery hypertension, and it is also a difficult problem to be tackled by clinical vasodilator in the treatment of pulmonary hypertension. Transforming growth factor B1 (transforming growth factor beta 1, TGF- beta 1) is a newly discovered cytokine that regulates cell growth and differentiation, in the promotion of fibrosis and tissue Structural remodeling has a significant role in the proliferation, hypertrophy, rearrangement, migration, apoptosis and the increase of extracellular matrix in the parenchymal cells of the vascular wall. The present study shows that the TGF- beta 1 protein, m RNA, is in the bronchial mucosa, lung tissue, pulmonary vascular wall and bronchoalveolar lavage fluid in the hypoxic induced chronic cor pulmonale animal models. It is suggested that hypoxia may lead to an increase in the expression level of TGF- beta 1. The activated TGF- beta 1 plays an important role in promoting the formation and development of pulmonary hypertension and cor pulmonale. Thus, it is suggested that the level of TGF- beta 1 in chronic cor pulmonale may also be elevated. This study measured 90 patients with chronic cor pulmonale in different cases. The expression level of serum TGF- beta 1 during the period (acute exacerbation and remission) and its correlation with arterial blood oxygen pressure (Pa O2) and pulmonary arterial hypertension, right ventricular enlargement, the main pulmonary artery internal diameter (MPAD), right ventricle diameter (RVD) and pulmonary artery systolic pressure (PASP) were analyzed to further explore the TGF- beta 1 in chronic pulmonary heart. Methods: 90 cases of acute exacerbation of chronic cor pulmonale, 62 men, 28 women, age 58~83 years, average age (69.77 + 7.24) years, regular treatment of symptoms, and signs and other conditions after the 2 weeks as remission group. Select the sex, age and other general data matching the health of healthy people in 90 cases. The serum TGF- beta 1 was measured by enzyme linked immunosorbent assay (ELISA), and the SPSS19.0 statistical software was applied to the acute exacerbation and remission period of one-way ANOVA. patients with color echocardiography. The parameters of MPAD, RVD, PASP were measured and Pa O2 was measured in parallel with arterial blood gas analysis. The above indexes were all with the level of serum TGF- beta 1. Results: 1. general data of 90 patients with acute exacerbation of chronic cor pulmonale, including 62 male and 28 female, average age (69.77 + 7.24) years, the average main pulmonary artery diameter (MPAD) was (25.97 + 3.37) mm, the mean right ventricle diameter was (26.43 + 2.99) mm, and the average systolic pressure of pulmonary artery (PASP) was (54.41 + 6.85) mm Hg The average main pulmonary artery diameter (MPAD) was (25.07 + 3.38) mm, the average right ventricle diameter was (26.45 + 3.67) mm, and the mean pulmonary artery systolic pressure (PASP) was (49.36 + 6.86) mm Hg. healthy control group, including 60 men and 30 women, with an average age of (68.90 + 3.38) years, and the average main pulmonary artery diameter (M). PAD) (19.13 + 2.84) mm, the mean right ventricular diameter was (20.31 + 4.11) mm.2. and TGF- beta 1 level TGF- beta 1 in the acute exacerbation of chronic cor pulmonale patients. The expression level of the serum in the remission stage and the healthy control group was (306.12 + 27.04) pg/ml, (161.16 + 24) pg/ml, and (82.15 + 24.34) pg/ml. three groups in the serum TGF- beta 1 level difference The levels of serum TGF- beta 1 and Pa O2 in patients with chronic pulmonary heart disease (P0.05).3. were negatively correlated with the level of TGF- beta 1 in the acute exacerbation and remission stage of chronic cor pulmonale patients (r=-0.739, P0.05; r=-0.619, P0.05). The serum levels of TGF- beta 1 in patients with chronic cor pulmonale and the right cardiac parameters of cardiac ultrasound, MPAD, RVD, PASP were correlated with the levels of TGF- beta 1 in the acute exacerbation period of chronic cor pulmonale patients with MPAD, RVD, PASP, and the level of serum beta 1 in the remission period was also positively correlated with the level of serum beta 1. R=0.718, P0.05, r=0.630, P0.05) conclusion: 1. the level of serum TGF- beta 1 in patients with chronic cor pulmonale was significantly higher than that in the healthy control group, and it was positively correlated with the ultrasound index of the pulmonary hypertension and the right ventricular enlargement, indicating that the TGF- beta 1 was very likely to be involved in the serum TGF- beta 1 level and Pa O2 of the chronic cor pulmonale patients with chronic cor pulmonale. Negative correlation shows that the elevated level of TGF- beta 1 may be significantly higher than the remission stage of serum TGF- beta 1 in patients with chronic pulmonary heart disease associated with.3. chronic cor pulmonale, suggesting that the monitoring of TGF- beta 1 can be used to evaluate the condition of chronic cor pulmonale patients. The observation of the curative effect provides a new level of serum TGF- beta 1 in patients with chronic cor pulmonale with.4.. Hyperoxia is closely related to hypoxia and right heart disease. Antagonizing TGF-beta 1 signaling pathway or inhibiting its activity may provide new ideas for the prevention and treatment of chronic pulmonary heart disease.
【學(xué)位授予單位】：承德醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R541.5

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