一氧化碳吸入对脂多糖诱导大鼠肺炎症细胞因子表达及损伤的影响

Effects of carbon monoxide inhalation on lung inflammatory cytokines and injuries in rats induced by lipopolysaccharide

目的观察低浓度一氧化碳（CO）吸入对脂多糖（LPS）诱导大鼠肺促炎、抗炎细胞因子表达及损伤的影响。方法72只雄性sD大鼠随机均分为对照组（吸入空气）、单纯吸入CO组、LPS（5mg／kg）注入组及LPS注入＋CO吸入4组。酶联免疫吸附法测定吸入气体1、3、6h后肺肿瘤坏死因子α（TNF—α）、白细胞介素6及10（IL-6、IL-10）含量，光镜下评分比较损伤变化。结果LPS注入组TNF—α、IL-6及损伤评分高于，IL—10低于相应时间点的对照组及单纯CO吸入组（P均〈0．05），组内各时间点比较，只有损伤评分随观察时程延长而增加（P均〈0．05）；LPS注入＋CO吸入组TNF—α、IL-6及损伤评分低于，IL—10高于相应时间点的LPS注入组（P均〈0.05），组内各时间点比较，差异无统计学意义（P〉0．05）；对照组与单纯CO吸入组间及组内各时间点比较，差异均无统计学意义（P〉0.05）。结论低浓度CO吸入以非时间依赖方式抑制LPS诱导大鼠肺促炎介质产生、增强抗炎因子表达而减轻损伤。

Objective To observe the effects of low concentration carbon monoxide （CO） inhalation on lung inflammatory cytokines and injuries in rats induced by lipopolysaccharide （LPS）. Methods Seventy-two male SD rats were randomly divided into control （exposed to room air）, 2. 5 × 10^-4（V/V） CO inhalation alone, 5 mg/kg LPS injection （exposed to room air） and 5 mg/kg LPS injection ＋ 2. 5 × 10^-4（V/V） CO inhalation groups. All rats were sacrificed by exsanguinations at 1, 3 and 6 h of exposure to gas. Lung lobes were harvested for measuring the levels of tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and interleukin-10 （IL-10） with enzyme-linked immunosorbent assay. The histopathology changes were observed with light microscopy. Results Compared with those of control or CO inhalation alone group at the same time point, the levels of TNF-α, IL-6, and injury score were increased and IL-10 level was decreased in LPS injection group （ all P 〈 0.05）. As compared with those of LPS injection group, the levels of TNF-α, IL-6, and injury score were decreased, while IL-10 level increased in LPS injection ＋ CO inhalation group （all P 〈0. 05）. Compared with those of the same group at the different time points, these parameters had no statistical differences except the injury score of LPS injection group was increased through time. Conclusion Carbon monoxide inhalation protects lung from LPS induced injury via reducing inflammatory mediators and increasing anti-inflammatory cytokines in rats, and these effects are independent of exposure time.