CAJ | 학술논문

目的:明确亚硝酸钠对急性肺损伤(ALI)的治疗作用及可能机制.方法:用脂多糖(LPS 4 mg/kg)气道滴入制备小鼠ALI模型.随机分为生理盐水组、LPS模型组、亚硝酸钠4.8 nmol/L、48 nmol/L、480 nmol/L治疗组.测定肺湿/干重比值、肺通透性,常规细胞形态学检测支气管肺泡灌洗液(BALF)中白细胞数量变化,苏木精曙红染色观察肺组织病理改变,用试剂盒检测肺组织白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、一氧化氮(NO)含量及一氧化氮合酶(NOS)活性.结果:腹腔注射4.8 nmol/L、48 nmol/L亚硝酸钠可明显降低LPS诱导的ALI小鼠肺湿/干重比值;减少BALF中的白细胞总数及中性粒细胞的比例;降低肺毛细血管通透性;改善肺组织病理变化;降低肺组织TNF-α/IL-10比值、抑制总NOS活性及诱导型NOS(iNOS)活性的增加.480 nmol/L亚硝酸钠对LPS诱导的ALI小鼠肺组织上述指标除NOS活性外,均无显著影响(P>0.05).与对照组相比,480 nmol/L亚硝酸钠显著增加了肺组织NO水平.结论:低、中剂量亚硝酸钠能够对抗LPS诱导的小鼠急性肺损伤,低剂量亚硝酸钠还原产生的NO对iNOS活性的抑制及下调TNF-α/IL-10比值可能在ALI中起重要作用.
목적:명학아초산납대급성폐손상(ALI)적치료작용급가능궤제.방법:용지다당(LPS 4 mg/kg)기도적입제비소서ALI모형.수궤분위생리염수조、LPS모형조、아초산납4.8 nmol/L、48 nmol/L、480 nmol/L치료조.측정폐습/간중비치、폐통투성,상규세포형태학검측지기관폐포관세액(BALF)중백세포수량변화,소목정서홍염색관찰폐조직병리개변,용시제합검측폐조직백세포개소-10(IL-10)、종류배사인자-α(TNF-α)、일양화담(NO)함량급일양화담합매(NOS)활성.결과:복강주사4.8 nmol/L、48 nmol/L아초산납가명현강저LPS유도적ALI소서폐습/간중비치;감소BALF중적백세포총수급중성립세포적비례;강저폐모세혈관통투성;개선폐조직병리변화;강저폐조직TNF-α/IL-10비치、억제총NOS활성급유도형NOS(iNOS)활성적증가.480 nmol/L아초산납대LPS유도적ALI소서폐조직상술지표제NOS활성외,균무현저영향(P>0.05).여대조조상비,480 nmol/L아초산납현저증가료폐조직NO수평.결론:저、중제량아초산납능구대항LPS유도적소서급성폐손상,저제량아초산납환원산생적NO대iNOS활성적억제급하조TNF-α/IL-10비치가능재ALI중기중요작용.
AIM: To investigate the effect of sodium nitrite (SN) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its underlying mechanism in mice. METHODS: All male Institute of Cancer Research (ICR) mice were randomly divided into five groups: Control group;LPS group;and SN 4.8 nmol/L, SN 48 nmol/L, SN 480 nmol/L (ip) groups. Lung wet weight/dry weight (W/D) ratio and permeability were detected. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF) was measured by cel1 counting and morphological changes in lung tissues were assayed by hematoxylin-eosin staining. The 1evels of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in lung were detected. Nitric oxide (NO) level and nitric oxide synthase (NOS) activity in lung were measured according to the specification. RESULTS: Compared to lung in LPS-induced ALI mice, at doses of 4.8 nmol/L and 48 nmol/L, not 480 nmol/L, SN markedly decreased the lung W/D ratio, total leukocyte number and neutrophil percentage in the BALF, lung permeability, and TNF-α/IL-10 ratio, in lung. SN at dose of 480 nmol/L markedly increased the lung NO level compared to control group. In addition, SN decreased the total NOS and inducible NOS (iNOS) activities compared to LPS-induced ALI mice. CONCLUSION: These results indicate that the protective effect of SN against LPS-induced ALI in mice is associated with the low dose SN-induced NO, as well as the subsequent decrease in iNOS activity and TNF-α/IL-10 ratio.