The effect of post-treatment N-acetylcysteine in LPS-induced acute lung injury of rats.
The effect of post-treatment N-acetylcysteine in LPS-induced acute lung injury of rats.
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DOI：
10.4046/trd.2012.73.1.22
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发表时间：
2012-07
影响因子：
2.9
通讯作者：
Kim YT
中科院分区：
文献类型：
--
作者：
Choi JS;Lee HS;Seo KH;Na JO;Kim YH;Uh ST;Park CS;Oh MH;Lee SH;Kim YT
氧化在急性肺损伤中起重要作用。本研究旨在探讨N-乙酰半胱氨酸(NAC)重复后处理对内毒素(LPS)诱导的大鼠急性肺损伤(ALI)的影响。选用6周龄雄性SD大鼠，随机分为4组。尾静脉注射脂多糖(EscherichiaColial5 mg/kg)。分别于内毒素注射后3h、6h、12h腹腔注射NAC(20 mg/kg)。于注射脂多糖后24小时取肺组织和支气管肺泡灌洗液(BALF)评价ALI。测定肺泡灌洗液中肿瘤坏死因子α和白细胞介素1β(IL 1β)的浓度。取肺组织测定核因子κB(NF-κB)、过氧化脂质(LPO)和髓过氧化物酶(MPO)。除主要实验外，每组均于72h行显微CT检查，以观察NAC的延迟效应。肺泡灌洗液中肿瘤坏死因子α和白介素1β浓度在内毒素组和NAC组之间无明显差异。NAC治疗组LPO浓度(5.5±2.8nmoL/mLvs.16.5±1.6nmoL/mLvs.16.5±1.6nmoL/mLvs.LPO)显著低于内毒素组(p=0.001)。NAC治疗组MPO活性明显低于脂多糖组(P<0.048)。NAC治疗组大鼠血清中的NF-κB浓度显著低于脂多糖组(P=0.0001)。Micro-CT显示NAC治疗组肺损伤程度较内毒素组轻。内毒素诱导ALI后，给予NaC治疗可通过抑制NF-κB的活化部分减轻ALI的程度。
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.