甘草黄酮对肺部炎症小鼠细胞因子表达和氧化反应的调节作用

Regulation of licorice flavonoids on cytokines mRNA expression and oxidation reaction in mice with lung inflammation

目的研究甘草黄酮对抗内毒素脂多糖(LPS)诱导小鼠肺部炎症的作用机制。方法小鼠气管内滴入LPS或生理盐水,6或24 h后取支气管肺泡灌洗液(BALF)和肺组织,测定BALF中的白细胞总数和中性粒细胞以及超氧化物歧化酶(SOD)活性,测定肺组织的含水量和病理变化,测定肺组织匀浆和BALF中的髓过氧化物酶(MPO)活性、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)的mRNA表达以及TNF-α蛋白水平。结果白细胞计数、肺含水量测定和肺组织病理检查等指标显示,小鼠气管内滴入LPS引起严重的肺部炎症。甘草黄酮给药后能预防LPS引起的这些变化。甘草黄酮能明显减少BALF中的总白细胞和中性粒细胞的数目,升高SOD活性。甘草黄酮能明显降低肺组织中的MPO活性,抑制TNF-α和IL-1βmRNA的表达,抑制TNF-α蛋白水平。结论甘草黄酮能改善LPS引起的小鼠肺部炎症,其抗炎作用可能与抑制细胞因子的表达和调节氧化/抗氧化反应有关。

Objective To study the mechanism of anti-inflammatory effects of licorice flavonoids （LF） isolated from the roots of Glycyrrhiza uralensis （licorice） on lipopolysaccharide （LPS）-induced lung inflammation in mice. Methods Mice were intratracheally instillated with either LPS （4 mg/kg） or saline. At 6 or 24 h after LPS intratracheal instillation, pathological examination and bronchoalveolar lavage were performed and the lung wet/dry weight ratio as an index of acute lung injury was assessed. Then, the numbers of total leukocytes, neutrophils and the activity of superoxide dismutase （SOD） and TNF-α protein in bronchoalveolar lavage fluid （BALF） were measured. LPS-induced myeloporoxidase （MPO） activity and expressions of TNF-α and IL-1β at the mRNA levels and TNF-α at the protein level in lung tissues were determined by RT-PCR and ELISA. Results LPS caused a severe lung inflammation, as indicated by the pathological findings and the lung wet/dry weight ratio. However, oral LF could attenuate these LPS-induced abnormalities. LF could decrease the numbers of total leukocyte cells and neutrophils, and increase the levels of SOD and TNF-α BALF. In addition, LF significantly suppressed the MPO activity, TNF-α and IL-1β mRNA expression levels, and TNF-α protein level in the lung tissues. Conclusion Inhibition of inflammatory cytokines expressions and regulation of oxidation/antioxidation of LF may be its anti-inflammatory mechanism in LPS-induced lung inflammation in mice.