唾液中游离皮质醇和松果体素水平昼夜节律性变化与夜间哮喘相关性研究

Alterations in chronobiology of salivary cortisol and melatonin in nocturnal asthma

目的 探讨唾液中游离皮质醇和松果体素水平昼夜节律性变化与夜间哮喘发病机制和昼夜肺功能变化的关系。方法 采用放射免疫分析方法测定 15例正常人和 15例夜间哮喘病人唾液中游离皮质醇和松果体素水平 ,哮喘病人中急性发作期 8例 ,缓解期 7例。 2 4h内按 12个时间点采集唾液样本 ,夜间取样时光照强度控制在 5 0lx之内。结果 3组间游离皮质醇水平差异具有显著性 (P <0 0 1)。与对照组比较 ,急性发作期和缓解期病人游离皮质醇 2 4h平均水平均降低 (P <0 0 1) ;振幅减小 (P <0 0 5 ) ;峰值相位(acrophase)延迟 (P <0 0 1,P <0 0 5 )。 3组间游离松果体素水平差异亦具有显著性 (P <0 0 1)。与对照组比较 ,急性发作期和缓解期病人松果体素水平基线值 ,振幅和峰值皆降低(P <0 0 5orP <0 0 1) ;急性发作期峰值相位延迟 (P <0 0 5 )。凌晨 4点游离皮质醇水平分别与占FEV1预计值 %和占PEF预计值 %正相关 (r =0 5 3 ,P <0 0 5 ;r =0 5 5 ,P<0 0 5 ) ,游离松果体素水平与占PEF预计值 %呈正相关 (r=0 5 2 ,P <0 0 5 )。昼夜占PEF预计值 %差值和夜间出现症状或憋醒次数呈正相关 (r =0 62 5 ,P <0 0 5 )。结论 唾液中游离皮质醇和松果体素水平的昼夜节律性改变参与夜间哮喘的发病过程 。

AIM To investigate the relationships between the alterations in circadian rhythms of cortisol, melatonin and nocturnal asthma METHODS Circadian rhythms of salivary free cortisol and melatonin levels were investigated in 15 control subjects and 8 exacerbation and 7 remission patients with bronchial asthma The serial salivary samples were collected at 12 time points during a 24 hour period The intensity of illumination was restricted to 50 lux during the night Salivary cortisol and melatonin levels were measured by radioimmunoassay RESULTS The 24 hour mean levels (mesor) of salivary cortisol was significantly different by one way ANOVA among the three groups ( P< 0 01) A significant lower of the mesor level was found in exacerbation and remission patients as compared with control subjects ( P< 0 01, P< 0 01, respectively) The acrophase was significant delayed in remission asthmatic patients ( P< 0 05), especially in exacerbation patients ( P< 0 01) The amplitude reduced significantly in exacerbation and remission asthmatic patients ( P< 0 05, P< 0 05,respectively) The results also showed that the salivary melatonin levels were significantly different among the three groups by one way ANOVA ( P< 0 01) The baseline, amplitude and peak level of salivary melatonin levels were significantly lower in exacerbation and remission asthmatic patients as compared with control subjects ( P<0 05, P<0 05; or P <0 01,respectively) The acrophase was significantly delayed in exacerbation asthmatic patients ( P< 0 05) At 04:00, there was a positive correlation between the levels of salivary cortisol and the % predicted FEV1 and the % predicted PEF ( r=0 53, P<0 05;r=0 55, P< 0 05, respectively), between the levels of salivary melatonin and the %predicted PEF( r=0 52, P< 0 05) in asthmatic patients A significant positive correlation was found between the overnight change of % predicted PEF (%Δpredicted PEF) and nocturnal symptoms or awakening times ( r=0 625, P< 0 05) CONCLUSIONS Our results suggested that melatonin might be involved in the pathogenesis of asthma Furthermore, the alterations of circadian rhythms of salivary cortisol and melatonin are closely associated with the worsening symptoms of asthma and the fall of lung function at midnight In addition, salivary melatonin and cortisol measurement are reliable, sensitive and easy method to monitor changes in the circadian rhythms