本文選題：TGF-β1 + IL-17　； 參考：《復旦大學》2012年碩士論文

【摘要】：研究背景支氣管哮喘是由多種炎癥細胞特別是肥大細胞、嗜酸性粒細胞和T淋巴細胞等共同參與的慢性氣道炎癥性疾病。盡管哮喘的發(fā)病機制尚未完全明了,目前認為Th2細胞占優(yōu)勢的Th1/Th2失衡是導致該病的一個重要發(fā)病機制。但近年來發(fā)現(xiàn),一些實驗和臨床現(xiàn)象并不能完全用Th1/Th2失衡理論來解釋。Th17細胞是近來發(fā)現(xiàn)的另一種CD4+T細胞的新亞型,其與哮喘有關,但是Th17細胞及其相關細胞因子在哮喘患者中的表達及與哮喘疾病之間的關系尚未明確,值得進一步深入研究。 目的 本研究目的通過檢測新發(fā)哮喘患者血清和誘導痰中TGF-β1、IL-17、IL-23指標及其它氣道炎癥指標,并與健康對照組相比；并比較新發(fā)哮喘患者吸入激素治療前后上述指標的變化,以明確哮喘患者TGF-β1、IL-17、IL-23表達的意義及氣道炎癥的變化。通過檢測規(guī)范治療后哮喘患者血清中TGF-β1、IL-17、IL-23指標及其它氣道炎癥指標,并比較肺功能不同阻塞程度哮喘患者之間上述指標的變化,以探討TGF-β1、IL-17、IL-23在哮喘患者氣道重塑中的意義。 方法 1采用病例對照方法,選取新發(fā)哮喘患者25例,同期選取27例健康人作為對照,記錄兩組人群的一般資料并收集血清標本,檢測兩組人群血清中TGF-β1、IL-17、IL-23的表達水平,比較兩組間各項指標的差異； 2采用自身前后對照方法,給予上述哮喘患者以吸入型糖皮質(zhì)激素(布地奈德200ug bid)治療3個月,檢測治療前后的ACT評分、肺功能、FENO水平,檢測治療前后血常規(guī)、血總IgE、誘導痰細胞計數(shù)、血清及誘導痰上清液中TGF-β1. IL-17.IL-23的表達水平,比較治療前后各項指標的差異： 3采用病例對照方法,收集規(guī)范治療至少3個月的哮喘患者91例。根據(jù)肺功能不同阻塞程度FEV1%作為分組標準,分為輕度組(FEV1%=80%).中度組(60%FEV1%80%)、重度組(FEV1%=60%),各組人數(shù)分別為27例、33例、31例。同期選取27例健康人作為對照。檢測并比較各組間血清中TGF-β1、IL-17、IL-23的表達水平及其它炎癥指標,以探討這些細胞因子在哮喘患者氣道重塑中的意義。 結果 1.新發(fā)哮喘患者與健康對照組相比,哮喘組血清TGF-β1的表達水平顯著高于對照組(1919.50±221.02pg/ml vs1450.41±366.54pg/ml,p=0.000):兩組間血清IL-17、IL-23的表達水平無統(tǒng)計學差異(4.57±1.05pg/ml vs4.57±0.80pg/ml, p=0.996；188.47±51.57pg/ml vs213.45±32.45pg/ml,p=0.877).哮喘組血清總IgE高于對照組(284.81±231.12ng/ml vs30.87±29.07ng/ml,p=0.001). 2.新發(fā)哮喘患者治療前后對比,治療后血清TGF-β1的表達水平較治療前明顯降低(1292.63±191.23pg/ml vs1919.50±221.02pg/ml,p=0.000)；治療后血清IL-17、 IL-23與治療前比較無統(tǒng)計學意義。治療后痰上清中TGF-β1、IL-17、IL-23的表達與治療前比較均無差異。治療后ACT評分顯著優(yōu)于治療前(22.16±4.53分vs14.96±4.25分,p=0.000)；治療后FEV1%顯著高于治療前(83.4%±15.74%vs72.45%±7.48%,p=0.002)；治療后FENO顯著低于治療前(49.98±25.98ppb vs109.18±65.23ppb,p=0.000)；治療后血Eos%明顯低于治療前(4.33%±1.89%vs5.7%±1.85%,p=0.004)；治療后血清總IgE顯著低于治療前(231.35±200.59ng/ml vs284.81±231.12ng/ml,p=0.004)；治療后誘導痰Eos%明顯低于治療前(6.58%±3.66%vs10.0%±4.75%,p=0.004)。治療前和治療后血清IL-17與血清IL-23、血清TGF-β1,血清IL-23與血清TGF-β1直線均不相關(p0.05)。治療前FENO與ACT評分呈負相關(r=-0.425,p=0.034)；與血Eos%直線不相關(p0.05),與痰Eos%正相關(r=0.657,p=0.020)。治療后FENO水平與FEV1%、ACT評分、血Eos%、痰Eos%直線均不相關(p0.05)。 3.經(jīng)規(guī)范化治療后哮喘組與健康對照組相比,哮喘組血清TGF-β1高于對照組(2168.50±377.03pg/ml vs1450.41±366.54pg/ml,p=0.000)；前者血清IL-17的表達水平顯著低于后者(3.78±0.93pg/ml vs4.57±0.80pg/ml,p=0.000)；兩組間血清IL-23差別無統(tǒng)計學意義(198.57±50.50pg/ml vs213.45±32.65pg/ml, p=0.080). 4.對肺功能不同阻塞程度的哮喘患者各組間比較,輕度組血清TGF-β1、IL-17與中度及重度組比較,差異有統(tǒng)計學意義(p0.05),中度與重度組比較差異無統(tǒng)計學意義。各組間血清IL-23的表達比較,差異均無統(tǒng)計學意義。各組間FENO比較,差異均無統(tǒng)計學意義。對各指標相關分析表明,血清IL-17與血清TGF-β1呈負相關(r=-0.306,p=0.004)；血清TGF-β1及血清IL-17均與血清IL-23無相關性(r==-0.151,p=0.154；r=0.164,p=0.121).FEV1%與血清TGF-β1呈負相關(r=-0.472,p=0.001)；與血清IL-17呈正相關(r=0.448,p=0.000)；與血清IL-23不相關。FENO與血清TGF-β1、IL-17、FEV1%直線均不相關；與血清IL-23負相關(r=-0.271,p=0.026)。 結論 1.TGF-β1在新發(fā)哮喘中較對照組明顯升高,ICS治療后較治療前下降；且在規(guī)范治療后的哮喘患者中,肺功能中重度減退組較輕度組高,血清TGF-β1與FEV1%呈負相關。表明TGF-β1是重要的氣道炎癥及重塑指標。 2.IL-17在新發(fā)哮喘中與對照組比較,及ICS治療前后比較,均無統(tǒng)計學意義；但在規(guī)范治療后的哮喘患者中,IL-17低于對照組,且肺功能中重度減退組較輕度組更低。表明IL-17是個復雜的細胞因子,可能起著雙向調(diào)節(jié)作用,持續(xù)氣道炎癥抑制其分泌和表達,使其在肺功能損害嚴重氣道重塑階段表達下降。 3.Th17細胞相關的細胞因子是個錯綜復雜的網(wǎng)絡,受各種因素及相互間影響,推測Thl7細胞在哮喘發(fā)病中其作用更加復雜多樣。 4.FENO是無創(chuàng)監(jiān)測氣道炎癥的重要指標,ICS治療后FENO較治療前明顯降低,且與ACT評分呈正相關。但FENO與FEV1%無相關性。
[Abstract]:Background bronchial asthma is a chronic airway inflammatory disease involving a variety of inflammatory cells, especially mast cells, eosinophils and T lymphocytes. Although the pathogenesis of asthma is not fully understood, the Th1/Th2 imbalance of the dominant Th2 cell is an important pathogenesis in recent years. It is found that some experimental and clinical phenomena do not fully use the Th1/Th2 imbalance theory to explain the recent discovery of.Th17 cells as a new subtype of CD4+T cells, which is associated with asthma, but the expression of Th17 cells and their associated cytokines in asthmatic patients and the relationship with asthma are not clear. It is worth further deepening. Research.
objective
The purpose of this study was to detect the TGF- beta 1, IL-17, IL-23 and other airway inflammation indexes in the serum and induced sputum of new asthmatic patients, and compare with the healthy control group, and compare the changes of these indexes before and after the treatment of inhaled hormone in new asthmatic patients, in order to clarify the significance of TGF- beta 1, IL-17, IL-23 expression and the changes of airway inflammation in asthmatic patients. To explore the significance of TGF- beta 1, IL-17, IL-23 in the airway remodeling of asthmatic patients by detecting the serum levels of TGF- beta 1, IL-17, IL-23, and other airway inflammation markers in the serum of patients with asthma after treatment.
Method
1 a case control method was used to select 25 new asthmatic patients and 27 healthy people in the same period as control. The general data of the two groups were recorded and the serum samples were collected to detect the expression level of TGF- beta 1, IL-17, IL-23 in the serum of two groups, and to compare the differences of the indexes among the two groups.
2 the asthma patients were treated with inhaled glucocorticoid (budesonide 200ug bid) for 3 months, and the ACT score, lung function, FENO level before and after treatment were detected. The blood routine, the total IgE, the induced sputum cell count, the expression of TGF- beta 1. IL-17.IL-23 in the induced sputum supernatant were measured before and after treatment. The differences of the indexes before and after the treatment were compared.
3 a case control method was used to collect 91 cases of asthma patients who had been treated for at least 3 months. According to the standard of FEV1%, the pulmonary function was divided into mild group (FEV1%=80%), moderate group (60%FEV1%80%) and severe group (FEV1%=60%), the number of each group was 27 cases, 33 cases, 31 cases, and 27 healthy people were selected as control. Test and comparison The levels of serum TGF- - 1, IL-17, IL-23 and other inflammatory markers were explored to explore the significance of these cytokines in airway remodeling in asthmatic patients.
Result
1. the expression level of serum TGF- beta 1 in the asthma group was significantly higher than that in the control group (1919.50 + 221.02pg/ml vs1450.41 + 366.54pg/ml, p=0.000) in the asthma group. There was no statistical difference between the two groups (4.57 + 1.05pg/ml vs4.57 + 0.80pg/ml, p=0.996, 188.47 + 51.57pg/ml). Ml, p=0.877). The total serum IgE in asthma group was higher than that in control group (284.81 + 231.12ng/ml vs30.87 + 29.07ng/ml, p=0.001).
2. compared before and after treatment, the expression level of serum TGF- beta 1 was significantly lower than before treatment (1292.63 + 191.23pg/ml vs1919.50 + 221.02pg/ml, p=0.000), and there was no significant difference between the serum IL-17 and IL-23 before treatment. The expression of TGF- beta 1, IL-17 and IL-23 in the sputum supernatant was not different from that before treatment. After treatment, the ACT score was significantly better than before treatment (22.16 + 4.53 vs14.96 + 4.25, p=0.000), and FEV1% was significantly higher than that before treatment (83.4% + 15.74%vs72.45% + 7.48%, p=0.002), and FENO was significantly lower than before treatment (49.98 + 25.98ppb vs109.18 + 65.23ppb, p=0.000); after treatment, the blood Eos% was significantly lower than before (4.33% + 49.98 1). .85%, p=0.004); serum total IgE was significantly lower than before treatment (231.35 + 200.59ng/ml vs284.81 + 231.12ng/ml, p=0.004). The induced sputum Eos% was significantly lower than before treatment (6.58% + 3.66%vs10.0% + 4.75%, p=0.004). Serum IL-17 and serum IL-23, serum beta 1, serum serum beta 1 lines were not related before and after treatment. P0.05). Before treatment, FENO was negatively correlated with ACT (r=-0.425, p=0.034); it was not related to the straight line of blood Eos% (P0.05), and positively correlated with Eos% (r=0.657, p=0.020).
3. after standardized treatment, the serum TGF- beta 1 in asthma group was higher than that in the control group (2168.50 + 377.03pg/ml vs1450.41 + 366.54pg/ml, p=0.000), and the level of serum IL-17 in the former was significantly lower than that of the latter (3.78 + 0.93pg/ml vs4.57 + 0.80pg/ml, p=0.000), and there was no statistically significant difference between the two groups (198.57 +. 50.50pg/ml vs213.45 + 32.65pg/ml, p=0.080).
4. compared with each group of asthmatic patients with different obstructive pulmonary function, the difference of serum TGF- beta 1, IL-17 and moderate and severe group was statistically significant (P0.05). There was no statistical difference between moderate and severe group. The difference of serum IL-23 expression in each group was not statistically significant. There was no difference in the difference of FENO in each group. The correlation analysis showed that serum IL-17 and serum TGF- beta 1 were negatively correlated (r=-0.306, p=0.004), and serum TGF- beta 1 and serum IL-17 were not related to serum IL-23 (r==-0.151, p=0.154; r=0.164, p=0.121).FEV1% and serum beta 1 were negatively correlated. There was no correlation between serum.FENO and serum IL-23, and serum TGF- IL-17 1, IL-17 and FEV1% were not correlated linearly with serum IL-23 (r=-0.271, p=0.026).
conclusion
1.TGF- beta 1 was significantly higher in the new asthma than that in the control group, and the ICS treatment was lower than that before the treatment. And in the asthmatic patients after the standard treatment, the moderate and severe pulmonary dysfunction group was higher than the mild group, and the serum TGF- beta 1 was negatively correlated with the FEV1%. It showed that TGF- beta 1 was an important airway inflammation and remodeling index.
2.IL-17 was compared with the control group in the new asthma group, and there was no statistical significance before and after the ICS treatment. But in the asthmatic patients after the standard treatment, IL-17 was lower than the control group, and the moderate and severe hypofunction group of the lung function was lower than the mild group. It showed that IL-17 was a complex cytokine that could play a two-way regulation and continue to inhibit the airway inflammation. Its secretion and expression reduced its expression in severe airway remodeling stage of lung function impairment.
The cytokine related to 3.Th17 cells is an intricate network. It is assumed that the role of Thl7 cells in the pathogenesis of asthma is more complex and complex due to various factors and the influence of each other.
4.FENO is an important index for non-invasive monitoring of airway inflammation. FENO after ICS treatment is significantly lower than that before treatment, and is positively correlated with ACT score. However, there is no correlation between FENO and FEV1%.

【學位授予單位】：復旦大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R562.25

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