Choi Jae Sung, Lee Ho Sung, Seo Ki Hyun, Na Ju Ock, Kim Yong Hoon, Uh Soo Taek, Park Choon Sik, Oh Mee Hye, Lee Sang Han, Kim Young Tong
Department of Internal Medicine, Clinical Research Institute, Soonchunhyang University College of Medicine, Cheonan, Korea.
Tuberc Respir Dis (Seoul). 2012 Jul;73(1):22-31. doi: 10.4046/trd.2012.73.1.22. Epub 2012 Jul 31.
Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats.
Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were measured in BALF. Nuclear factor κB (NF-κB), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC.
TNF-α and IL-1β concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5±2.8 nmol/mL vs. 16.5±1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4±1.8 unit/g vs. 11.2±6.3 unit/g, tissue) (p<0.048). The concentration of NF-κB in NAC treatment group was significantly lower than that of LPS group (0.3±0.1 ng/µL vs. 0.4±0.2 ng/µL) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group.
After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-κB activation.
氧化在急性肺损伤中起重要作用。本研究旨在阐明N-乙酰半胱氨酸（NAC）重复后处理对脂多糖（LPS）诱导的大鼠急性肺损伤（ALI）的影响。
将六周龄雄性Sprague-Dawley大鼠分为4组。通过尾静脉静脉注射LPS（大肠杆菌5mg/kg）。在LPS注射后3、6和12小时腹腔注射NAC（20mg/kg）。在LPS注射后24小时获取支气管肺泡灌洗液（BALF）和肺组织以评估ALI。测定BALF中肿瘤坏死因子α（TNF-α）和白细胞介素1β（IL-1β）的浓度。使用肺组织测定核因子κB（NF-κB）、脂质过氧化（LPO）和髓过氧化物酶（MPO）。在与主要实验相隔72小时时检查每组的微型计算机断层扫描（micro-CT）图像，以观察NAC的延迟效应。
LPS组和NAC治疗组BALF中TNF-α和IL-1β浓度无差异。NAC治疗组的LPO浓度显著低于LPS组（5.5±2.8nmol/mL对16.5±1.6nmol/mL）（p = 0.001）。NAC治疗组的MPO活性显著低于LPS组（6.4±1.8单位/克对11.2±6.3单位/克，组织）（p<0.048）。NAC治疗组的NF-κB浓度显著低于LPS组（0.3±0.1ng/μL对0.4±0.2ng/μL）（p = 0.0001）。Micro-CT显示NAC治疗组的肺损伤程度低于LPS组。
在用脂多糖诱导ALI后，NAC的治疗性给药通过抑制NF-κB活化部分减轻了ALI的程度。
