Maghsadi Zahra, Azadmehr Abbas, Moghadamnia Ali Akbar, Feizi Farideh, Hamidi Negar
Student Research Committee, Babol University of Medical Sciences, Babol, I.R. Iran.
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, I.R. Iran.
Res Pharm Sci. 2023 Jan 19;18(2):177-184. doi: 10.4103/1735-5362.367796. eCollection 2023 Apr.
Pulmonary fibrosis (PF) is a chronic and life-threatening interstitial lung disease. N-acetyl cysteine (NAC) is an antioxidant pharmaceutically available to reduce endothelial dysfunction, inflammation, and fibrosis, however, the therapeutic effect of NAC on PF has not been clearly identified. This research aimed to investigate the possible therapeutic impact of NAC on PF induced by bleomycin in the rat model.
Rats received intraperitoneal injections of NAC at 150, 300, and 600 mg/kg for 28 days before bleomycin, while the positive and negative control groups were treated with bleomycin alone and normal saline, respectively. Then, rats' lung tissues were isolated and leukocyte infiltration and also collagen deposition were evaluated using hematoxylin and eosin and Mallory trichrome stainings, respectively. In addition, the levels of IL-17, and TGF-β cytokines in bronchoalveolar lavage fluid and hydroxyproline in homogenized lung tissues were assayed using the ELISA method.
FINDINGS/RESULTS: Histological findings indicated that NAC decreased leukocyte infiltration, collagen deposition, and fibrosis score in the bleomycin-induced PF tissue. Moreover, NAC significantly reduced TGF-β and hydroxyproline levels at 300-600 mg/kg, as well as IL-17 cytokine at 600 mg/kg.
NAC showed a potential anti-fibrotic effect by reducing hydroxyproline and TGF-β as well as an anti-inflammatory effect by decreasing IL-17 cytokine. So, it may be administered as a prophylactic or therapeutic candidate agent to attenuate PF immunomodulatory effects. Although, future studies are suggested.
肺纤维化（PF）是一种慢性且危及生命的间质性肺疾病。N-乙酰半胱氨酸（NAC）是一种可用于减轻内皮功能障碍、炎症和纤维化的抗氧化剂，但NAC对PF的治疗效果尚未明确。本研究旨在探讨NAC对博来霉素诱导的大鼠PF模型可能的治疗作用。
在给予博来霉素前28天，大鼠分别腹腔注射150、300和600mg/kg的NAC，而阳性和阴性对照组分别单独给予博来霉素和生理盐水。然后，分离大鼠肺组织，分别用苏木精-伊红染色和马洛里三色染色评估白细胞浸润和胶原沉积。此外，采用ELISA法检测支气管肺泡灌洗液中IL-17和TGF-β细胞因子水平以及肺组织匀浆中羟脯氨酸水平。
组织学结果表明，NAC可减少博来霉素诱导的PF组织中的白细胞浸润、胶原沉积和纤维化评分。此外，NAC在300 - 600mg/kg时可显著降低TGF-β和羟脯氨酸水平，在600mg/kg时可显著降低IL-17细胞因子水平。
NAC通过降低羟脯氨酸和TGF-β显示出潜在的抗纤维化作用，并通过降低IL-17细胞因子显示出抗炎作用。因此，它可能作为一种预防性或治疗性候选药物来减轻PF的免疫调节作用。不过，建议开展进一步研究。
