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目的探讨低浓度二氧化硫(sulfurdioxide,SO2)暴露对哮喘大鼠CD4+CD 25+调节性T细胞(regulatory T cells,Treg)数量及转录因子Foxp3表达的影响.方法将60只雄性Wistar大鼠按随机数字表法分为正常对照组、低浓度SO2暴露组、哮喘组和低浓度SO2暴露哮喘组,每组15只;哮喘组采用卵清白蛋白(OVA)致敏并吸入激发制备哮喘模型,正常对照组吸入雾化生理盐水,低浓度SO2暴露组采用吸入低浓度SO2,低浓度SO2暴露哮喘组于每日雾化激发OVA前给予低浓度SO2吸入.采用流式细胞术检测外周血CD4+CD 25+Treg细胞占CD4+T细胞的比例,酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测外周血和肺组织γ-干扰素(interferon-γ,γ-INF)以及白细胞介素-4(interleukin-4,IL-4)含量;Western blot检测肺组织Foxp3蛋白表达水平.结果哮喘组大鼠CD4+CD 25+Treg为(5.78±1.26)%,低于正常对照组的(9.63±1.37)%;低浓度SO2暴露哮喘组为(3.15±0.82)%,低于正常对照组和哮喘组,差异有统计学意义(P均<0.01).哮喘组大鼠血浆和肺组织中IL-4含量[(23.51±4.86)ng/L和(0.93±0.16)ng/L]高于正常对照组[(11.24±2.53)ng/L和(0.29±0.06)ng/L],差异有统计学意义(P均<0.01);低浓度SO2暴露哮喘组血浆和肺组织中IL-4含量[(36.73±7.46)ng/L和(1.67±0.41)ng/L]高于正常对照组和哮喘组,差异有统计学意义(P均<0.01);哮喘组血浆和肺组织中γ-INF含量[(63.82±21.78)ng/L和(0.49±0.15)ng/L]低于正常对照组[(156.98±60.23)ng/L和(1.58±0.18)ng/L],差异有统计学意义(P<0.01),低浓度SO2暴露哮喘组γ-INF含量[(10.02±1.68)ng/L和(0.43±0.12)ng/L]低于正常对照组和哮喘组,差异有统计学意义(P<0.01).哮喘组Foxp3蛋白表达为(8.23±0.56),低于正常对照组的(11.87±0.65)(P<0.05);低浓度SO2暴露哮喘组为(6.05±0.36),低于正常对照组和哮喘组(P<0.05).结论低浓度SO2暴露可能通过下调CD4+CD 25+Treg数量并抑制Foxp3蛋白表达,进一步加重哮喘的Th1/Th2比例失衡,可能是诱发哮喘发病的因素.“,”Objective To investigate the effect of low level sulfurdioxide(SO2)exposure on the amount of CD4+CD25+ regulatory T cells(Treg)and expression of transcription factor Foxp3 in asthmatic rats.Methods Sixty male Wistar rats were divided into 4 groups(n=15 for each group)according to randomdigits table,they were normal control group,SO2 exposure group,asthmatic group(by inhaleing aerosolized ovalbumin)and combined OVA and SO2 exposure group.8 weeks later,the percentage of CD4+CD25+ T cells was determined by flow cytometry analysis,the levels of interleukin-4(IL-4)and interferon-γ(γ-INF)in peripheral blood and lung homogenates were measured by enzyme linked immunosorbent assay(ELISA),while the protein expression of Foxp3 in the lung tissues was detected by Western blot.Results The percentage of CD4+CD25+T cells in asthmatic group(5.78±1.26)%was significantly lower than that of normal control group[(9.63±1.37)%,P<0.01],this percentage in low level SO2 exposure plus asthmatic group(3.15±0.82)%was remarkably lower than that of normal control group and asthmatic group(P<0.01).IL-4 levels both in plasma(23.51±4.86)ng/L and lung(0.93±0.16) ng/L were significantly increased in asthmatic rats compared with normal control group[(11.24±2.53)ng/L and(0.29±0.06)ng/L respectively,P<0.01];the levels mentioned above in SO2 exposed group[(36.73±7.46)ng/L and(1.67±0.41)ng/L,respectively]were also significantly higher than that of control and asthmatic groups(P<0.01).The γ-INF levels of plasma(63.82±21.78)ng/L and lung tissues(0.49±0.15)ng/L in asthmatic group significantly decreased compared with the normal control group[(156.98±60.23) ng/L and(1.58±0.18)ng/L,respectively,P<0.01],and these levels in asthmatic plus SO2 group[(10.02±1.68)ng/L and(0.43±0.12)ng/L]were all significantly lowered compared with asthmatic group and normal control group(P<0.01).As for protein expression of Foxp3,the level in asthmatic group(8.23±0.56)was lower than that of normal control group(11.87±0.65,P<0.05),while the level in asthmatic plus SO2 group(6.05±0.36)was also lower than that of normal control group and asthmatic group(P<0.05).Conclusion The results suggested that low level SO2 exposure may down regulate the amount of CD4+CD25+Treg cells and inhibite the expression of Foxp3,thereby further aggravate the disbalance of Th1/Th2 ratio in asthma,which may be one of the important factors to trigger asthma seizures.