黄芪对脂多糖诱导的小鼠急性肺损伤作用机制的研究

Study on the mechanism of radix astragali on lipopolysaccharide-induced acute lung injury in mice

目的通过气管内滴注脂多糖建立小鼠急性肺损伤模型,探讨黄芪对急性肺损伤的保护作用及其疗效评估。方法将小鼠随机分为正常对照组(气管内滴注无菌PBS 60μl)、模型组(LPS组,气管内滴注0.5 mg/kg,LPS100μl,作用24 h)、黄芪治疗组(0.75 g/L RA+LPS组),观察小鼠肺组织病理学改变、支气管肺泡灌洗液(BALF)中细胞计数变化、测定蛋白含量及超氧化物歧化酶(SOD)活性。分离肺组织以评估湿/干重比,Western blot法检测促炎细胞因子的mRNA表达和组织学变化。结果与模型组相比,黄芪治疗组BALF中总细胞数及蛋白质含量比值明显降低(P<0.01);黄芪治疗组小鼠右肺中叶W/D比值明显降低(P<0.01);小鼠血清SOD活性含量明显高于模型组(P<0.01)。在肺泡灌洗液检测中发现,与模型组相比,黄芪治疗组TNF-α、IL-1β、IL-6含量明显降低,差异有统计学意义(P<0.01)。病理组织学提示黄芪治疗组可显著减轻肺组织损伤。结论黄芪能够显著减轻LPS诱导的肺部炎症,对小鼠急性肺损伤有很强的保护作用。

Objective To establish a mouse model of acute lung injury by intratracheal instillation of lipopolysaccharide,and to explore the protective effect of radix astragali on acute lung injury and the evaluation of curative effect.Methods The mice were randomly divided into the normal control group(intratracheal instillation of 60μl of sterile PBS),the model group(LPS group,intratracheal instillation of 0.5 mg/kg,100μl of LPS for 24 h)and the radix astragali treatment group(0.75 g/L RA+LPS group).The histopathological changes of lung tissue,the changes of cell count in bronchoalveolar lavage fluid(BALF)were observed.The protein content and the activity of superoxide dismutase(SOD)were measured.Lung tissues were isolated to assess the wet/dry weight ratio.The mRNA expression and histological changes of proinflammatory cytokines were detected by Western blot.Results Compared with LPS model group,the total cell count and protein content ratio in BALF of radix astragali treatment group were significantly decreased(P<0.01).The W/D ratio in the right middle lobe of mice in radix astragali treatment group was significantly decreased(P<0.01).The SOD activity content in serum of mice in radix astragali treatment group was significantly higher than that of LPS group(P<0.01).The bronchoalveolar lavage fluid examination found that the contents of TNF-α,IL-1β,and IL-6 were significantly lower in the radix astragali treatment group compared with the model group(P<0.01),and the differences were statistically significant(P<0.01).Histopathology suggested that the astragalus treatment group significantly reduced lung tissue injury.Conclusion Radix astragali can significantly reduce LPS-induced pulmonary inflammation and has a strong protective effect on acute lung injury in mice.