Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
Regina Elena National Cancer Institute, Thoracic Surgery Unit, Rome, Italy.
Biomed Pharmacother. 2018 Jul;103:1-8. doi: 10.1016/j.biopha.2018.04.011. Epub 2018 Apr 24.
N-Acetylcysteine (NAC) reduces the risk of exacerbation of chronic obstructive pulmonary disease (COPD). Although NAC also has anti-inflammatory activity, the detailed mechanism leading to its protective role remains to be elucidated. We tested the impact of NAC against the effects of lipopolysaccharide (LPS) in an ex vivo model of COPD exacerbation, and investigated the role of neurokinin A (NKA) in this context.
Isolated airways from COPD patients were incubated overnight with LPS (100 ng/ml). NAC was tested at concentrations resembling the plasma levels elicited by oral administration of NAC at 200 mg/day (very low dose), 600 mg/day (low dose) and 1.200 mg/day (high dose).
NAC at high concentrations normalized the peroxidase activity, HO, malondialdehyde (MDA), nitric oxide, glutathione (GSH), total antioxidant capacity (TAC), and interleukin 6 (IL-6) (overall change 34.32% ± 4.22%, P < 0.05 vs. LPS-treated). NAC at low concentrations modulated peroxidase activity, HO, MDA, GSH, TAC, and IL-6 (overall change 34.88% ± 7.39%, P < 0.05 vs. LPS-treated). NAC at very-low concentrations was effective on peroxidase activity, HO, GSH, and IL-6 (overall change 35.05 ± 7.71%, P < 0.05 vs. LPS-treated). Binary logistic regression analysis indicated that the modulatory effect of NAC on NKA levels was associated with a reduction of pro-oxidant factors and IL-6, and selectively blocking the NK receptor abolished such an association.
This study demonstrates that, along with its well-known antioxidant activity, the protective effect of NAC against the detrimental effect of LPS is due to the modulation of NKA and IL-6 levels.
N-乙酰半胱氨酸（NAC）可降低慢性阻塞性肺疾病（COPD）恶化的风险。尽管 NAC 也具有抗炎活性，但导致其保护作用的详细机制仍有待阐明。我们在 COPD 恶化的体外模型中测试了 NAC 对抗脂多糖（LPS）的影响，并在此背景下研究了神经激肽 A（NKA）的作用。
将 COPD 患者的离体气道孵育过夜，并用 LPS（100ng/ml）处理。以类似于口服 200mg/天 NAC （低剂量）和 1200mg/天 NAC （高剂量）产生的血浆浓度测试 NAC。
高浓度的 NAC 使过氧化物酶活性、HO、丙二醛（MDA）、一氧化氮、谷胱甘肽（GSH）、总抗氧化能力（TAC）和白细胞介素 6（IL-6）恢复正常（总变化 34.32%±4.22%，P<0.05 与 LPS 处理组相比）。低浓度的 NAC 调节过氧化物酶活性、HO、MDA、GSH、TAC 和 IL-6（总变化 34.88%±7.39%，P<0.05 与 LPS 处理组相比）。非常低浓度的 NAC 对过氧化物酶活性、HO、GSH 和 IL-6 有效（总变化 35.05%±7.71%，P<0.05 与 LPS 处理组相比）。二元逻辑回归分析表明，NAC 对 NKA 水平的调节作用与减少促氧化剂因子和 IL-6 有关，选择性阻断 NK 受体消除了这种关联。
本研究表明，除了其众所周知的抗氧化活性外，NAC 对 LPS 有害作用的保护作用还归因于 NKA 和 IL-6 水平的调节。
