背景:慢性阻塞性肺疾病(COPD)是非特异性慢性炎症性肺疾病,尚无治愈方法。党参(CR)已被证明具有抗炎和抗氧化作用。因此,本研究旨在探讨不同CR品种对COPD小鼠的潜在抗炎作用。
方法:60只雄性无特殊病原体(SPF)级C57BL/6J小鼠随机分为6组,每组10只小鼠。采用香烟烟雾提取物(CSE)联合脂多糖(LPS)诱导COPD小鼠模型,各组小鼠给予相应的药物。在所有小鼠中评估肺功能。肺组织用苏木精-伊红(HE)染色,Masson,和周期性酸洗(PAS)染色,采用酶联免疫吸附试验(ELISA)检测血清白细胞介素(IL)-8和肿瘤坏死因子(TNF)-α水平。Further,比色法检测血清和肺组织丙二醛(MDA)和超氧化物歧化酶(SOD)水平。网络药理学和分子对接用于预测信号通路,通过蛋白质印迹分析验证。
结果:与COPD组相比,每个CR给药组的小鼠血清IL-8和TNF-α水平显着降低,血清和肺组织MDA水平,和病理性肺组织损伤,肺功能和SOD水平升高(P<0.01)。Westernblot分析还表明p-p65/p65和p-IκB-α/IκB-α蛋白表达显著下调,在CR处理的小鼠的肺组织中Nrf2蛋白表达显著上调(P<0.01)。
结论:总之,CR有效增强肺功能,最大限度地减少肺组织损伤,并抑制COPD小鼠的炎症和氧化应激。此外,这些发现表明,抑制Nrf2/NF-κB轴可能是CR缓解COPD的关键作用机制。
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a nonspecific chronic inflammatory lung disease with no known cure. Codonopsis Radix (CR) has been shown to exhibit anti-inflammatory and antioxidant effects. Therefore, this study aimed to investigate the potential anti-inflammatory effects of different CR varieties on COPD mice.
METHODS: Sixty male-specified pathogen-free grade C57BL/6J mice were randomly divided into 6 groups, 10 mice in each group. The COPD mice model was induced by cigarette smoke extract combined with lipopolysaccharide, and the mice in each group were given corresponding drugs. Lung function was assessed in all mice. Lung tissues were stained with hematoxylin-eosin, Masson, and periodic acid-Schiff stains, and serum levels of interleukin (IL)-8 and tumor necrosis factor (TNF)-α were detected using an ELISA. Further, serum and lung tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric assay. Network pharmacology and molecular docking were used to predict signaling pathways, which were validated by Western blot analysis.
RESULTS: Compared with the COPD group, the mice in each dosing group of CR exhibited significant reductions in serum IL-8 and TNF-α levels, serum and lung tissue MDA levels, and pathological lung tissue damage, alongside elevations in lung function and SOD levels (p < 0.01). Western blot analysis also indicated significant downregulation of p-p65/p65 and p-IκB-α/IκB-α protein expression, alongside significant upregulation of Nrf2 protein expression in the lung tissues of mice treated with CR (p < 0.01).
CONCLUSIONS: In summary, CR effectively enhances lung function, minimizes lung tissue damage, and inhibits inflammation and oxidative stress in mice with COPD. Additionally, these findings suggest that inhibition of the Nrf2/NF-κB axis may be a key mechanism of action of CR in the alleviation of COPD.