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The Role Of Oxidative Stress-JAK/STAT Signaling Pathway In Asthma Exacerbations Induced By PM2.5

Posted on:2016-12-27Degree:MasterType:Thesis
Country:ChinaCandidate:X Y MaFull Text:PDF
GTID:2284330479992532Subject:Public health
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Objective: To investigate the seasonal impact of Taiyuan city PM2.5 on inflammatory factors of patients with asthma and to explore oxidative stress- JAK/STAT signaling pathway could participate in the regulation of atmospheric PM2.5 induced asthma chronic inflammation, which helps deeply elucidate the relationship between PM2.5 and asthma exacerbation, then provide novel thoughts for modulation mechanism of asthmatic inflammation.Methods: 29 patients with asthma were selected from three communities in Taiyuan city as the research object, using the panel method. In 2013 March, June, September, the concentration of PM2.5 in their own living environment were monitored respectively, their blood samples were collected and isolated peripheral blood lymphocytes at the same time. The expression levels of oxidative stress index in plasma MDA, T-SOD, T-AOC and inflammatory factor index in plasma IL-5, IL-6, IL-12, COX-2, Eotaxin were detected by ELISA. The fluorescence quantitative PCR was used to determine the m RNA levels of tyrosine kinase(JAK1, JAK2, JAK3) and transcription factors(STAT4, STAT6).Results: 1. PM2.5 concentrations in patients with asthma living environment in three seasons were higher than the daily average concentration of PM2.5 standard, and the spring> summer> autumn(P <0.05). The concentration of plasma MDA in patients with asthma in spring was higher than in summer and autumn(P < 0.001), T-SOD, T-AOC concentration is lower than the summer and autumn(P < 0.001). Compared to summer and autumn, the m RNA levels of JAK2 and STAT4 appeared a downward trend in spring, but the expression of JAK3 m RNA appeared a raise trend(P<0.05). The m RNA levels of JAK3in spring and summer were higher than in autumn(P<0.05). The concentration of IL-5 and Eotaxin in patients with asthma in spring was higher than summer and autumn(P < 0.05), the concentration of IL-6 and COX-2 in spring was higher than that in autumn(P < 0.05), the concentration of IL-12 in spring is lower than in summer and autumn(P < 0.05). 2. Adjusted for age, gender, BMI factors in patients with asthma, using mixed effects model we analyzed the relationship between outdoor, indoor and individual PM2.5 exposure and each index of patients with asthma: PM2.5 exposure was positively correlated with MDA(βout PM2.5=0.012, P=0.0078; βindividual PM2.5=0.010, P=0.0033); and negatively correlated with T-AOC(βout PM2.5=-0.020, P=0.0089; βinner PM2.5=-0.021, P=0.0018; βindividual PM2.5=-0.022, P=0.0005);and negatively correlated with T-SOD(βout PM2.5=-0.082, P=0.047). Outdoor, indoor, the individual PM2.5 was positively correlated with IL-6(βo u t P M 2. 5=0.021, P=0.037; βi n d o o r P M 2. 5=0.018, P=0.072; βi n d i v i d u a l P M 2. 5=0.016, P=0.084);and positively correlation with the COX-2(βindoor PM2.5=0.13, P<0.0001; βindividual PM2.5=0.12, P<0.0001);and positively correlation with the Eotaxin(βout PM2.5=0.020, P=0.0012; βindoor PM2.5=0.0091, P=0.034); And negatively correlation with IL-12(β室外 PM2.5=-0.13, P=0.077; β室内 PM2.5=-0.23, P=0.0012; β个体 PM2.5=-0.15, P=0.017). 3. Adjusted for age, gender, BMI factors in patients with asthma, using mixed effects models oxidative stress index(MDA, T-AOC, T-SOD) influenced on expression of JAK m RNA in patients with asthma: MDA was negatively correlated with JAK1 m RNA, JAK2 m RNA; MDA was positively correlated with JAK3 m RNA. T-AOC was positively correlated with JAK1 m RNA, JAK2 m RNA, negatively correlated with JAK3 m RNA; T-SOD was positively correlated with JAK1 m RNA, JAK2 m RNA, negatively correlated with JAK3 m RNA. 4. Adjusted for age, gender, BMI factors in patients with asthma, using mixed models we analyzed the relationship between the expression of m RNA(JAK1, JAK2, JAK3) and the expression of m RNA(STAT4, STAT6) m RNA : JAK2 was positively correlated with STAT4(β=0.39, P=0.0007), but the expression of JAK2 was negatively correlated with STAT6 expression(β=-0.16, P=0.0085), JAK3 was negatively correlated with STAT4, but JAK3 was positively correlated with STAT6(β=0.14,P=0.0035). 5. Adjusted for age, gender, BMI factors in patients with asthma, using mixed modelswe found that STAT6 was positively correlated with IL-5(β=1.19, P=0.0052); STAT4 was positively correlated with IL-12(β=5.36, P=0.023).Conclusions: 1. Th1/Th2 imbalance exists in asthma patients, which is associated with seasonal variation; High PM2.5 exposure in spring could aggravate asthmatic chronic inflammation. 2. Oxidative stress-JAK/STAT signaling pathway may be involved in asthma exacerbation induced by PM2.5, and regulate the asthmatic inflammation.
Keywords/Search Tags:PM2.5, asthma, oxidative stress, JAK-STAT, cytokines
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