N-乙酰半胱氨酸治疗慢性阻塞性肺疾病患者疗效和作用机制研究

Effect and mechanism of NAC on patients with chronic obstructive pulmonary disease

目的探讨N-乙酰半胱氨酸(NAC)治疗慢性阻塞性肺疾病(COPD)的临床疗效和作用机制。方法将78例COPD患者随机分为治疗组和对照组,观察其治疗前后对痰液炎症细胞计数及核因子-kB(NF-kB)、白细胞介素8(IL-8)、肿瘤坏死因子α(TNF-α)水平的影响,以及对临床症状、肺功能指标和血丙二醛(MDA)、全血超氧化物歧化酶(SOD)和血清血管紧张素Ⅰ转换酶(ACE)活性及血内皮素-1(ET-1)含量的变化情况,并与20名健康人作比较。结果78例COPD患者中脱落5例(治疗组3例,对照组2例)。NAC治疗COPD的总显效率为72.50%,总有效率为87.50%,与对照组比较有显著性差异(P<0.05)。与对照组比较,治疗组能明显改善肺功能指标(FEV1、FVC、mPAP)和血MDA、SOD、ACE活性及ET-1含量(P<0.05)。治疗后治疗组痰液中性粒细胞(PMN)、非中性粒细胞(mPMN);IL-8、TNF-α和NF-kB活性(A值)较治疗前显著降低(P<0.01),降低作用优于对照组(P<0.05),治疗期间未见明显毒副作用。结论NAC治疗COPD患者可改善其临床症状和肺功能,安全性良好,通过增强抗氧化能力和减轻COPD患者气道炎症反应而发挥其治疗作用。

AIM： To explore the clinical effect and mechanism of NAC on patients with chronic obstructive pulmonary disease （ COPD ）. METHODS： 78 patients with COPD in stable phase were randomly divided into the treated group and the control group. Total and differential count of inflammatory cell in sputum, NF-kB, IL-8, TNF-α, and clinical symptom, FVC, FEV1, mPAP and the blood levels of malondialdchyde （MDA）, superoxide dismutase （SOD）, angiotensin-converting enzyme （ACE） and endothelins-1 （ET-1） were measured before and after treatment. RESULTS：5 cases of the 78 patients dropped out. The rate of total marked effect and total effect were 72.50%, and 87.50% respectively, in the treated group. All the indexes measured in patients before and after treatment were significantly different from those in healthy subjects （ P 〈 0.05）. Differential count of polymorphonuclear neutrophil （PMN）, the levels of IL-8 and TNF-α, the activity of NF-kB in sputum in the treated group decreased after treatment （P 〈 0.01）, while the FEV1, FVC, mPAP, MDA, SOD, ACE, and ET-1 were ameliorated （P 〈 0.05）, and all were better than those in the control group （ P 〈 0.05）. No obvious adverse effects were found. CONCLUSION： NAC used for treating COPD is able to relive the clinical symptom and improve the lung function, with a fairly good safety, and can play a therapeutic role on patients with COPD by way of increasing anti-oxidative ability and reducing the airway inflammatory reaction.