支气管哮喘患儿脂氧化酶及其产物脂氧素A4和白三烯C4的变化及临床意义

摘要

目的 了解不同程度支气管哮喘(简称哮喘)患儿白细胞15-脂氧化酶、5-脂氧化酶、血液脂氧素A4(lipoxin A4,LXA4)及白三烯C4(leukotriene C4,LTC4)水平的变化.方法 根据哮喘诊断标准及分度标准选取哮喘患儿106例作为哮喘组,检测前4周均无感染性疾病或其他脏器疾病;选取既往健康的学校体检正常儿童40名作为对照组.应用RT-PCR方法测定急性发作期的轻、中、重度哮喘息儿血白细胞15-脂氧化酶、5-脂氧化酶的mRNA表达,应用ELISA方法测定哮喘患儿血液LXA4、LTC4含量.观察患儿在吸入速效β2受体激动剂后的呼气峰流速(PEF)及FEV1与血液LXA4及LTC4的关系.结果 轻、中、重度哮喘息儿白细胞15-脂氧化酶相对表达量分别为1.78±0.56、1.28±0.45和0.58±0.22(F=16.72,P<0.01),血液LXA4分别为(5.52±1.97)、(1.86±0.72)和(0.81±0.36)μg/L(F=22.59,P<0.01),均逐渐降低,但仍分别高于对照组的15-脂氧化酶相对表达量(0.26±0.12,P<0.05)和血液LXA4[(0.04±0.01)μg/L,P<0.05],患儿PEF与FEV1的减少与血液LXA4呈正相关.而轻、中、重度哮喘患儿白细胞5-脂氧化酶相对表达量分别为0.26±0.12、0.79±0.34和1.21±0.52(F=18.64,P<0.01),血液LTC4分别为(22.4±8.2)、(54.6±28.4)和(118.7±41.1)ng/L(F=25.91,P<0.01),逐渐升高,均分别高于对照组的5-脂氧化酶相对表达量(0.12±0.05)和血液LTC4[(6.8±2.5)ng/L,均P<0.05],PEF与FEV1的减少与血液LTC4呈负相关.结论 LXA4是白三烯的天然生理拮抗物质.哮喘患儿随着病情加重,体内15-脂氧化酶及其产物LXA4不足;5-脂氧化酶及其产物LTC4水平的升高,可能是哮喘加重的原因之一.%Objective To investigate the expressions of 15- and 5-lipoxygenases in leukocytes and the changes of the levels of blood lipoxin A4 (LXA4 ) and leukotriene C4 ( LTC4) in children with asthma. Methods The mRNA levels of 15- and 5-lipoxygenases in leukocytes were assessed by RT-PCR, and the levels of blood LXA4 and LTC4 were determined by ELISA, in 106 children with mild, moderate and severe asthma. Forty healthy children served as the controls. Results In children with mild, moderate and severe asthma, the relative mRNA levels of 15-lipoxygenase in leukocytes were 1.78 ±0.56, 1.28 ±0.45 and 0. 58 ±0. 22 (F = 16. 72, P <0. 01), respectively, and all were higher than that of the controls (0. 26 ± 0.12, P<0.05). The levels of blood LXA4 were (5.52±1.97), (1. 86 ±0.72) and (0. 81 ±0. 36) μg/L (F =22. 59, P <0.01), respectively, decreasing with the severity of asthma, and all were higher than that of the controls [ (0. 04 ±0. 01) μg/L, P <0. 05]. There was a positive correlation between PEF, FEV, and blood LXA4. The relative levels of 5-lipoxygenase mRNA in leukocytes were 0. 26 ±0. 12, 0. 79 ±0. 34 and 1. 21 ±0. 52,respectively in children with asthma of mild, moderate and severe degree(F = 18. 64, P <0. 01) ,which showed an increase with the severity of the disease, and all of which were higher than that of thecontrols (0.12 ±0.05, P< 0.05). The levels of blood LTC4 were (22.4 ± 8. 2 ), (54.6±28.4) and (118. 7 ±41. 1) ng/L ( F = 25. 91, P < 0.01), respectively, also showing an increase with the severity of asthma, and were higher than that of the controls [ (6. 8 ± 2. 5 ) ng/L, P < 0. 05 ]. There was a negative correlation between PEF, FEV, and blood LTC4. Conclusion The reversed changes of 15-lipoxygenase product LXA4 and 5-lipoxygenase product LTC4 in children with asthma of mild, moderate and severe degree suggests that insufficiency of LXA4, an physiological antagonist to leukotrienes, and an overproduction of LTC4 , may be involved in the pathogenesis of worsening of asthma in children.