【摘要】：目的:通過檢測對比慢性阻塞性肺病急性加重期與穩(wěn)定期患者、健康患者血清IL-21、IL-17、IL-6、RORγt的表達(dá)并分析其與疾病嚴(yán)重程度及臨床相關(guān)指標(biāo)的關(guān)系,進(jìn)一步研究IL-21-RORγt-IL-21、IL-17炎癥反應(yīng)軸、IL-6/IL-21-肺動脈軸與慢性阻塞性肺病的炎癥反應(yīng)、肺氣腫、肺血管病變的關(guān)系,為慢性阻塞性肺病的研究提供新的理論基礎(chǔ)和方向。方法:選取2015年9月-2016年9月到青島大學(xué)附屬醫(yī)院呼吸內(nèi)科就診的COPD的患者120例,其中急性加重期患者60例作為急性期組,穩(wěn)定期患者60例作為穩(wěn)定期組;同期健康查體的患者60例作為健康對照組。所有患者均晨起抽取空腹靜脈血,用酶聯(lián)免疫法測定血清IL-21、IL-17、IL-6、RORγt的含量,并測定患者FEV1、FVC、FEV1/FVC、肺動脈內(nèi)徑、肺動脈壓力、右心室的內(nèi)徑等指標(biāo)。探討三組數(shù)據(jù)之間上述指標(biāo)的差異,用spss22進(jìn)行統(tǒng)計(jì)學(xué)分析。結(jié)果:1.IL-21、IL-17、IL-6、RORγt血清IL-21的含量在急性加重期組為279.107±17.836 pg/ml,穩(wěn)定期組為224.109±30.051 pg/ml,對照組為170.201±25.197 pg/ml,急性加重組高于穩(wěn)定期組及健康對照組(t=11.8、26.63,P0.05),穩(wěn)定期組表達(dá)顯著高于健康對照組(t=10.34,P0.05)。血清IL-17的含量在急性加重期組為145.114±19.961 pg/ml,穩(wěn)定期組為49.830±7.735 pg/ml,對照組為25.819±4.376 pg/ml,急性期組顯著高于穩(wěn)定期組、健康對照組(t=33.34、44.07,P0.05),穩(wěn)定期組顯著高于對照組(t=20.35,P0.001)。血清IL-6的含量在急性加重期組為39.414±3.225 pg/ml,穩(wěn)定期組為32.598±3.475pg/ml,對照組為24.831±2.121 pg/ml,急性期組顯著高于穩(wěn)定期組、健康對照組(t=10.81、28.52,P0.05),穩(wěn)定期組高于對照組(t=14.31,P0.05)。各組血清RORγt的含量在急性加重期組3.206±0.263 ng/ml,穩(wěn)定期組為2.527±0.469ng/ml,對照組為2.095±0.271 ng/ml,急性期組顯著高于穩(wěn)定期組(t=8.33、18.4,P0.05)。穩(wěn)定期組顯著高于對照組(t=2.69,P0.05)。2.三組呼吸功能的檢測在FEV1、FEV1/FVC方面,急性加重期低于穩(wěn)定期組及健康對照組,穩(wěn)定期低于健康對照組,三組差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。在FVC方面,急性加重期FVC較健康對照組略有下降(P0.05)。3.血清C-反應(yīng)蛋白、血沉、D-二聚體的表達(dá)在血清C-反應(yīng)蛋白方面,急性加重期與穩(wěn)定期及健康對照組相比存在顯著差異,穩(wěn)定期高于健康對照組,三組差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。血沉在三組數(shù)據(jù)之間未見明顯差異。急性加重期D-二聚體高于穩(wěn)定期及正常期,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。4.肺動脈內(nèi)徑、肺動脈壓力、右心室內(nèi)徑肺動脈內(nèi)徑的測定結(jié)果為,急性加重期27.05±2.708 mm,穩(wěn)定期24.98±1.833 mm,健康對照組23.77±1.851 mm,急性加重期與穩(wěn)定期及健康對照組相比存在顯著統(tǒng)計(jì)學(xué)差異(P0.05),穩(wěn)定期的肺動脈內(nèi)徑高于健康對照組(P0.05)。肺動脈壓力的測定結(jié)果為,急性加重期52.64±9.064 mm Hg,穩(wěn)定期42.82±7.510 mm Hg,健康對照組28.85±2.641 mm Hg,急性加重期與穩(wěn)定期及健康對照組相比存在顯著差異(P0.05),穩(wěn)定期的肺動脈壓力高于健康對照組(P0.05)。右心室內(nèi)徑測定結(jié)果為,急性加重期28.42±3.731mm,穩(wěn)定期26.41±3.218mm,健康對照組25.91±3.878mm,急性加重期高于健康對照組,存在顯著統(tǒng)計(jì)學(xué)差異(P0.05)。穩(wěn)定期高于正常期(P0.05)。5.COPD合并肺動脈高壓組、COPD不合并合并肺動脈高壓組與健康對照組之間IL-21的表達(dá)IL-21測定結(jié)果為,急性加重期273.26±23.45 pg/ml,穩(wěn)定期230.88±39.02 pg/ml,健康對照組170.84±25.34 pg/ml。IL-6測定結(jié)果為,急性加重期為37.32±4.76pg/ml,穩(wěn)定期為34.48±4.79 pg/ml,健康對照組為24.73±2.13 pg/ml,IL-21與IL-6在急性加重期均顯著高于穩(wěn)定期及健康對照組,穩(wěn)定期的表達(dá)高于健康對照組(P0.05)。肺動脈壓力的測定結(jié)果,急性加重期為56.23±6.89 mm,穩(wěn)定期40.31±5.30 mm,健康對照組28.81±2.59 mm。肺動脈平均內(nèi)徑的測定結(jié)果為,急性加重期26.61±2.59 mm,穩(wěn)定期25.51±2.34 mm,健康對照組23.72±1.89 mm,急性加重期與穩(wěn)定期及健康對照組存在顯著差異,穩(wěn)定期高于健康對照組,數(shù)值具有統(tǒng)計(jì)學(xué)差異(P0.05)。6.相關(guān)分析血清IL-21與IL-17、IL-6、RORγt呈顯著正相關(guān)(r=0.795、0.775、0.686,P0.05),與CRP呈顯著正相關(guān)(r=0.611,P0.05);與FEV1/FVC、FEV1呈負(fù)相關(guān)(r=-0.729、-0.830,P0.05);與肺動脈平均內(nèi)徑、肺動脈壓力呈顯著正相關(guān)(r=0.448、0.802,P0.05)。結(jié)論:1.慢性阻塞性肺病患者血清IL-21表達(dá)明顯增高,在COPD急性加重期更加顯著,且IL-6、IL-17、RORγt呈顯著正相關(guān),提示IL-21參與到COPD的氣道炎癥過程中。IL-21可能通過IL-21-RORγt(TH17)-IL-17軸在慢性阻塞性肺病疾病進(jìn)展過程中發(fā)揮重要作用,說明IL-21參與了COPD的炎癥反應(yīng)過程,并且起到一定的促炎作用,起到橋梁的作用。2.IL-21與氣流受限指標(biāo)FEV1/FVC呈顯著負(fù)相關(guān),與疾病嚴(yán)重程度指標(biāo)FEV1呈負(fù)相關(guān),提示IL-21參與了氣流受限的過程,隨著IL-21的表達(dá)量增加,疾病逐漸加重。3.COPD伴或不伴肺動脈高壓與健康對照組IL-21、IL-6表達(dá)存在顯著差異,且IL-21與IL-6、肺動脈平均內(nèi)徑、肺動脈壓力呈顯著正相關(guān),提示IL-21通過IL-6/IL-21-肺血管途徑參與了肺動脈血管改變、肺動脈高壓形成的過程。
[Abstract]:Objective: To investigate the expression of IL-21, IL-17, IL-6 and ROR-gamma t in serum of patients with chronic obstructive pulmonary disease (COPD) at acute exacerbation stage and stable stage, and the relationship between IL-21-ROR-gamma t-IL-21, IL-17 inflammatory response axis, IL-6/IL-21 pulmonary artery axis and COPD. Methods: From September 2015 to September 2016, 120 patients with COPD were selected from the Department of Respiratory Medicine, Qingdao University Affiliated Hospital. Among them, 60 patients in acute exacerbation stage were treated as acute stage group and 60 patients in stable stage were treated as stable stage. All the patients got up in the morning and measured the levels of IL-21, IL-17, IL-6 and ROR gamma t by ELISA. The indexes of FEV1, FVC, FEV1/FVC, pulmonary artery diameter, pulmonary artery pressure and right ventricular diameter were also measured. Results: 1. The serum levels of IL-21, IL-17, IL-6 and ROR gamma t in the acute exacerbation group were 279.107 (+ 17.836) pg/ml, 224.109 (+ 30.051) pg/ml in the stable phase group and 170.201 (+ 25.197) pg/ml in the control group. The levels of IL-21, IL-17, IL-6 and ROR gamma t in the acute exacerbation group were higher than those in the stable phase group and the healthy control group (t = 11.8, 26.63, P 0.05). The level of serum IL-17 in acute exacerbation group was 145.114 (+19.961) pg/ml, stable phase group was 49.830 (+7.735) pg/ml, control group was 25.819 (+4.376) pg/ml, acute phase group was significantly higher than stable phase group, healthy control group (t = 33.34, 44.07, P 0.05), stable phase group was significantly higher than control group (t = 20.35, P 0.0.05). The serum levels of IL-6 in acute exacerbation group were 39.414+3.225 pg/ml, 32.598+3.475 pg/ml in stable phase group, 24.831+2.121 pg/ml in control group, significantly higher in acute phase group than in stable phase group, healthy control group (t = 10.81, 28.52, P 0.05), stable phase group was higher than that in control group (t = 14.31, P 0.05). 206 + 0.263 ng / ml, 2.527 + 0.469 ng / ml in stable phase group, 2.095 + 0.271 ng / ml in control group, significantly higher in acute phase group than in stable phase group (t = 8.33, 18.4, P 0.05). Respiratory function of stable phase group was significantly higher than that of control group (t = 2.69, P 0.05). 2. Respiratory function of three groups in FEV1, FEV1 / FVC was lower in acute exacerbation phase than that of stable phase group and healthy control group. The levels of serum C-reactive protein, erythrocyte sedimentation rate and D-dimer in acute exacerbation were significantly higher than those in stable and healthy control groups (P 0.05). There was no significant difference in ESR among the three groups. D-dimer in acute exacerbation was higher than that in stable and normal period. The difference was statistically significant (P 0.05). 4. The pulmonary artery diameter in the stable phase was higher than that in the healthy control group (P 0.05). The pulmonary artery pressure in the stable phase was higher than that in the stable phase (P 0.05). The pulmonary artery pressure in the stable phase was higher than that in the healthy control group (P Stable phase was higher than normal phase (P 0.05). 5. The expression of IL-21 in COPD patients with pulmonary hypertension and COPD patients without pulmonary hypertension was 273.26 (+ 23.45) pg/ml in acute exacerbation, 230.88 (+ 39.02) pg/ml in stable phase and 170.2 pg/ml in healthy control group. The results of IL-6 assay showed that the acute exacerbation stage was 37.32+4.76pg/ml, the stable stage was 34.48+4.79 pg/ml, the healthy control group was 24.73+2.13 pg/ml, the expressions of IL-21 and IL-6 in the acute exacerbation stage were significantly higher than those in the stable stage and healthy control group, and the expression of IL-6 in the stable stage was higher than that in the healthy control group (P 0.05). The mean internal diameter of pulmonary artery in the acute exacerbation stage was 26.61 (+ 2.59 mm), the stable stage was 25.51 (+ 2.34 mm) and the healthy control group was 23.72 (+ 1.89 mm). There were significant differences between the acute exacerbation stage and the stable stage and the healthy control group. Correlation analysis showed that serum IL-21 was positively correlated with IL-17, IL-6 and ROR gamma t (r = 0.795, 0.775, 0.686, P 0.05), and positively correlated with CRP (r = 0.611, P 0.05); negatively correlated with FEV1 / FVC, FEV1 (r = - 0.729, - 0.830, P 0.05); positively correlated with mean diameter of pulmonary artery and pulmonary artery pressure (r = 0.448, 0.802, P 0.05). Conclusion: 1. The expression of serum IL-21 in COPD patients was significantly increased, especially in acute exacerbation of COPD. IL-6, IL-17 and ROR-gamma T were positively correlated, suggesting that IL-21 was involved in the airway inflammation of COPD. IL-21 may play an important role in the progression of COPD through the IL-21-ROR-gamma t (TH17) -IL-17 axis. Interleukin-21 participated in the inflammatory process of COPD and played a role in promoting inflammation and bridging. 2. IL-21 was negatively correlated with airflow limitation index FEV1 / FVC, and negatively correlated with disease severity index FEV1, suggesting that IL-21 participated in the process of airflow limitation, with the increase of IL-21 expression, the disease gradually aggravated.3. COPD. The expression of IL-21 and IL-6 was significantly correlated with IL-6, mean pulmonary artery diameter and pulmonary artery pressure, suggesting that IL-21 participated in the process of pulmonary artery changes and pulmonary hypertension formation through the IL-6/IL-21 pulmonary vascular pathway.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R563.9

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