Th17细胞相关细胞因子在支气管哮喘气道炎症及重塑中的意义

发布时间：2018-05-01 11:12

本文选题：TGF-β1 + IL-17　；参考：《复旦大学》2012年硕士论文

【摘要】：研究背景支气管哮喘是由多种炎症细胞特别是肥大细胞、嗜酸性粒细胞和T淋巴细胞等共同参与的慢性气道炎症性疾病。尽管哮喘的发病机制尚未完全明了,目前认为Th2细胞占优势的Th1/Th2失衡是导致该病的一个重要发病机制。但近年来发现,一些实验和临床现象并不能完全用Th1/Th2失衡理论来解释。Th17细胞是近来发现的另一种CD4+T细胞的新亚型,其与哮喘有关,但是Th17细胞及其相关细胞因子在哮喘患者中的表达及与哮喘疾病之间的关系尚未明确,值得进一步深入研究。目的本研究目的通过检测新发哮喘患者血清和诱导痰中TGF-β1、IL-17、IL-23指标及其它气道炎症指标,并与健康对照组相比；并比较新发哮喘患者吸入激素治疗前后上述指标的变化,以明确哮喘患者TGF-β1、IL-17、IL-23表达的意义及气道炎症的变化。通过检测规范治疗后哮喘患者血清中TGF-β1、IL-17、IL-23指标及其它气道炎症指标,并比较肺功能不同阻塞程度哮喘患者之间上述指标的变化,以探讨TGF-β1、IL-17、IL-23在哮喘患者气道重塑中的意义。方法 1采用病例对照方法,选取新发哮喘患者25例,同期选取27例健康人作为对照,记录两组人群的一般资料并收集血清标本,检测两组人群血清中TGF-β1、IL-17、IL-23的表达水平,比较两组间各项指标的差异； 2采用自身前后对照方法,给予上述哮喘患者以吸入型糖皮质激素(布地奈德200ug bid)治疗3个月,检测治疗前后的ACT评分、肺功能、FENO水平,检测治疗前后血常规、血总IgE、诱导痰细胞计数、血清及诱导痰上清液中TGF-β1. IL-17.IL-23的表达水平,比较治疗前后各项指标的差异： 3采用病例对照方法,收集规范治疗至少3个月的哮喘患者91例。根据肺功能不同阻塞程度FEV1%作为分组标准,分为轻度组(FEV1%=80%).中度组(60%FEV1%80%)、重度组(FEV1%=60%),各组人数分别为27例、33例、31例。同期选取27例健康人作为对照。检测并比较各组间血清中TGF-β1、IL-17、IL-23的表达水平及其它炎症指标,以探讨这些细胞因子在哮喘患者气道重塑中的意义。结果 1.新发哮喘患者与健康对照组相比,哮喘组血清TGF-β1的表达水平显著高于对照组(1919.50±221.02pg/ml vs1450.41±366.54pg/ml,p=0.000):两组间血清IL-17、IL-23的表达水平无统计学差异(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).哮喘组血清总IgE高于对照组(284.81±231.12ng/ml vs30.87±29.07ng/ml,p=0.001). 2.新发哮喘患者治疗前后对比,治疗后血清TGF-β1的表达水平较治疗前明显降低(1292.63±191.23pg/ml vs1919.50±221.02pg/ml,p=0.000)；治疗后血清IL-17、 IL-23与治疗前比较无统计学意义。治疗后痰上清中TGF-β1、IL-17、IL-23的表达与治疗前比较均无差异。治疗后ACT评分显著优于治疗前(22.16±4.53分vs14.96±4.25分,p=0.000)；治疗后FEV1%显著高于治疗前(83.4%±15.74%vs72.45%±7.48%,p=0.002)；治疗后FENO显著低于治疗前(49.98±25.98ppb vs109.18±65.23ppb,p=0.000)；治疗后血Eos%明显低于治疗前(4.33%±1.89%vs5.7%±1.85%,p=0.004)；治疗后血清总IgE显著低于治疗前(231.35±200.59ng/ml vs284.81±231.12ng/ml,p=0.004)；治疗后诱导痰Eos%明显低于治疗前(6.58%±3.66%vs10.0%±4.75%,p=0.004)。治疗前和治疗后血清IL-17与血清IL-23、血清TGF-β1,血清IL-23与血清TGF-β1直线均不相关(p0.05)。治疗前FENO与ACT评分呈负相关(r=-0.425,p=0.034)；与血Eos%直线不相关(p0.05),与痰Eos%正相关(r=0.657,p=0.020)。治疗后FENO水平与FEV1%、ACT评分、血Eos%、痰Eos%直线均不相关(p0.05)。 3.经规范化治疗后哮喘组与健康对照组相比,哮喘组血清TGF-β1高于对照组(2168.50±377.03pg/ml vs1450.41±366.54pg/ml,p=0.000)；前者血清IL-17的表达水平显著低于后者(3.78±0.93pg/ml vs4.57±0.80pg/ml,p=0.000)；两组间血清IL-23差别无统计学意义(198.57±50.50pg/ml vs213.45±32.65pg/ml, p=0.080). 4.对肺功能不同阻塞程度的哮喘患者各组间比较,轻度组血清TGF-β1、IL-17与中度及重度组比较,差异有统计学意义(p0.05),中度与重度组比较差异无统计学意义。各组间血清IL-23的表达比较,差异均无统计学意义。各组间FENO比较,差异均无统计学意义。对各指标相关分析表明,血清IL-17与血清TGF-β1呈负相关(r=-0.306,p=0.004)；血清TGF-β1及血清IL-17均与血清IL-23无相关性(r==-0.151,p=0.154；r=0.164,p=0.121).FEV1%与血清TGF-β1呈负相关(r=-0.472,p=0.001)；与血清IL-17呈正相关(r=0.448,p=0.000)；与血清IL-23不相关。FENO与血清TGF-β1、IL-17、FEV1%直线均不相关；与血清IL-23负相关(r=-0.271,p=0.026)。结论 1.TGF-β1在新发哮喘中较对照组明显升高,ICS治疗后较治疗前下降；且在规范治疗后的哮喘患者中,肺功能中重度减退组较轻度组高,血清TGF-β1与FEV1%呈负相关。表明TGF-β1是重要的气道炎症及重塑指标。 2.IL-17在新发哮喘中与对照组比较,及ICS治疗前后比较,均无统计学意义；但在规范治疗后的哮喘患者中,IL-17低于对照组,且肺功能中重度减退组较轻度组更低。表明IL-17是个复杂的细胞因子,可能起着双向调节作用,持续气道炎症抑制其分泌和表达,使其在肺功能损害严重气道重塑阶段表达下降。 3.Th17细胞相关的细胞因子是个错综复杂的网络,受各种因素及相互间影响,推测Thl7细胞在哮喘发病中其作用更加复杂多样。 4.FENO是无创监测气道炎症的重要指标,ICS治疗后FENO较治疗前明显降低,且与ACT评分呈正相关。但FENO与FEV1%无相关性。
[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%.

【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R562.25

【参考文献】