【摘要】 血红素氧合酶(hemeoxygenase,HO)降解血红素的主要代谢产物一氧化碳(carbonmonoxide,CO)具有抗氧化、抗炎症和抑制细胞凋亡作用,而脂多糖(lipopolysaccharide,LPS)诱导的肺组织过氧化、炎症性损伤及大量肺泡上皮和血管内皮细胞凋亡正是导致肺损伤(lunginjury,LI)的关键。由此我们猜想,CO有可能通过上述机制对LI起保护作用。通过静脉注入LPS(5mg/kg体重)诱导大鼠LI,观察吸入室内空气或2.5×10-4(V/V)CO3h后,肺氧化酶学、炎症细胞因子、细胞凋亡、HO-1表达及组织形态学变化。结果显示,静脉注入LPS诱导LI后,CO吸入组大鼠肺肿瘤坏死因子α(tumornecrosisfactor-α,TNF-α)、白细胞介素6(interlukin-6,IL-6)、丙二醛(maleicdialdehyde,MDA)、髓过氧化物酶(myeloperoxidase,MPO)和细胞凋亡分别为(0.91±0.25)pg/mg蛋白、(0.64±0.05)pg/mg蛋白、(1.02±0.23)nmol/mg蛋白、(7.18±1.62)U/mg蛋白、(1.60±0.34)%,均显著低于LI组的(1.48±0.23)pg/mg蛋白、(1.16±0.26)pg/mg蛋白、(1.27±0.33)nmol/mg蛋白、(8.16±1.49)U/mg蛋白、(3.18±0.51)%(P<0.05)。CO吸入组HO-1、白细胞介素10(interlukin-10,IL-10)表达和超氧化物歧化酶(superoxidedismutase,SOD)活性分别为(5.43±0.92)、(0.26±0.07)pg/mg蛋白、(60.09±10.21)U/mg蛋白,它们均显著高于LI组的(3.08±0.82)、(0.15±0.03)pg/mg蛋白、(50.98±6.88)U/mg蛋白(P<0.05)。与LI组相比,CO吸入组肺损伤减轻。研究结果表明,低浓度CO吸入通过抗氧化、抗炎症、抑制细胞凋亡、上调HO-1表达而减轻LPS诱导的肺损伤。更多还原

【Abstract】 Carbon monoxide (CO), a metabolite of heme catalysis by heme oxygenase (HO), has been proposed to have anti-oxidative,anti-inflammatory and anti-apoptotic functions. Lipopolysaccharide (LPS)-induced lung injury (LI) is characterized by oxidativestress, inflammatory reaction and excessive pulmonary cell apoptosis. So we supposed that CO might have protection against LI. LIin rats was induced by intravenous injection of LPS (5 mg/kg). To observe the effect of CO inhalation, LI rats were exposed to 2.5×10-4(V/V) CO for 3 h. CO-induced changes of lung oxidative stress parameters, inflammatory cytokines, cell apoptosis, HO-1 expressionand histology were examined. Results revealed that expressions of the tumor necrosis factor-α (TNF-α) and interlukin-6 (IL-6),activities of maleic dialdehyde (MDA) and myeloperoxidase (MPO), and cell apoptosis in LPS injection + CO inhalation group were(0.91±0.25) pg/mg protein, (0.64±0.05) pg/mg protein, (1.02±0.23) nmol/mg protein, (7.18±1.62) U/mg protein and (1.60±0.34)%,respectively, significantly lower than the corresponding values in LI group [(1.48±0.23) pg/mg protein, (1.16±0.26) pg/mg protein,(1.27±0.33) nmol/mg protein, (8.16±1.49 ) U/mg protein and (3.18±0.51) %, P<0.05]. Moreover, CO inhalation obviously increasedthe expressions of HO-1 and interlukin-10 (IL-10) and activity of superoxide dismutase (SOD) [(5.43±0.92), (0.26±0.07) pg/mgprotein and (60.09±10.21) U/mg protein in LPS injection + CO inhalation group vs (3.08±0.82), (0.15±0.03) pg/mg protein and (50.98±6.88) U/mg protein in LI group, P<0.05]. LI was attenuated by CO inhalation. Our study demonstrates that inhalation of lowconcentration of CO protects lung against LPS-induced injury via anti-oxidant, anti-inflammation, anti-apoptosis and up-regulation ofHO-1 expression.更多还原