褪黑素对稳定期中重度慢性阻塞性肺疾病患者氧化应激和炎症反应的影响

The effect of melatonin on oxidative stress and inflammatory reaction in patients with moderate to severe chronic obstructive pulmonary disease and its mechanisms

目的探讨褪黑素治疗对稳定期中重度慢性阻塞性肺疾病(COPD)患者氧化应激和炎症反应的影响并探讨其机制。方法 42例稳定期中重度COPD患者分为褪黑素组和安慰剂组,每组各21例,分别接受褪黑素(3 mg/d)或安慰剂治疗,持续3个月。对比分析患者在治疗前及治疗后2、3个月3个时间点血浆中8-异前列腺素、白细胞介素-8(IL-8)、肿瘤坏死因子α(TNF-α)和超敏C反应蛋白(h-CRP)的浓度、肺功能、6 min步行实验和MRC呼吸困难评分。结果治疗2个月后,褪黑素组血浆中的8-异前列腺素较安慰剂组显著降低(10.40±5.4 vs.16.92±4.33,P<0.05),IL-8较安慰剂组显著降低(6.88±2.37 vs.11.33±3.39,P<0.05)。治疗3个月后,褪黑素组血浆中8-异前列腺素、IL-8的浓度较安慰剂组显著降低,分别为(9.40±4.0 vs.17.92±3.33,P<0.01)、(5.67±3.22 vs.9.31±3.23,P<0.05);褪黑素组患者血浆中8-异前列腺素、IL-8的浓度较治疗前显著降低,分别为(9.40±4.0 vs.20.40±8.4,P<0.01)、(5.67±3.22vs.12.33±3.88,P<0.05)。褪黑素组患者TNF-α浓度、h-CRP浓度较安慰剂组显著降低,分别为(25.83±9.18 vs.35.83±12.18,P<0.05)、(1.76±1.18 vs.3.09±1.79,P<0.05)。3个月后,褪黑素组患者呼吸困难评分较安慰剂组显著改善(1.56±1.38 vs.2.09±1.16,P<0.05),两组患者在肺功能和6 min步行实验结果无统计学差异。结论褪黑素降低稳定期COPD患者血液中的8-异前列腺素、IL-8、TNF-α和h-CRP的浓度,改善患者呼吸困难评分。褪黑素对稳定期中重度COPD患者在降低氧化应激和抑制炎症反应上作用显著,显示其对COPD具有潜在的治疗价值。

Objective To investigate the effect of melatonin on oxidative stress and inflammatory reaction in patients with moderate to severe chronic obstructive pulmonary disease and to explore its mechanisms.Methods 42 patients with moderate to severity chronic obstructive pulmonary disease in stable stage were randomly divided into melatonin group and control group,and 21 patients in each group treated with melatonin(3 mg/d)or placebo for 3 months respectively.The plasma levels of 8-isoprotane,IL-8,TNF-α,h-CRP pulmonary function,six minutes walking test and MRC dyspnea score before treatment,2 months and 3 months after the treatment were analyzed.Results After 2 months of treatment,compared to placebo groups,melatonin could significantly decrease the concentration of 8-isoprotane(10.40±5.4 vs.16.92±4.33,P<0.05),and the concentration of IL-8(6.88±2.37 vs.11.33±3.39,P<0.05).After 3 months of treatment,compared to placebo groups,melatonin could significantly decrease the concentration of 8-isoprotane(9.40±4.0 vs.17.92±3.33,P<0.01),and IL-8(5.67±3.22 vs.9.31±3.23,P<0.05).Compared with before treatment,melatonin could significantly decreased the concentration of 8-isoprotane(9.40±4.0 vs.20.40±8.4,P<0.01)and IL-8(5.67±3.22 vs.12.33±3.88,P<0.05)after 3 months.Meanwhile,the concentration of the TNF-α(25.83±9.18 vs.35.83±12.18,P<0.05)and hypersensitive C(1.76±1.18 vs.3.09±1.79,P<0.05)reactive protein in the melatonin group was greatly lower than the placebo group.After 3 months,compared to the placebo group,MRC dyspnea score of patients in the group of melatonin was improved significantly(1.56±1.38 vs.2.09±1.16,P<0.05),and lung function and six minutes walk test showed no significant difference between patients in the two groups.Conclusions Exogenous melatonin administration can decrease the concentration of 8-isoprotane,IL-8,TNF-αand h-CRP in the blood of patients with moderate to severe COPD,and improve the MRC dyspnea score.Melatonin has a significant effect on reducing oxidative stress and inhibiting inflammatory reaction in patients with moderate and severe stage stable COPD,which demonstrates its potential therapeutic value with broad clinical application prospects.