银杏叶提取物联合泼尼松对慢性阻塞性肺疾病小鼠Ghrelin-Obestatin信号通路的影响

Effects of Ginkgo Folium Extract Combined with Prednisone on Ghrelin-Obestatin Signaling Pathway in Mice with Chronic Obstructive Pulmonary Disease

关键词:  慢性阻塞性肺疾病  银杏叶提取物  泼尼松  Ghrelin-Obestatin信号通路  小鼠

Key words:  chronic obstructive pulmonary disease  Ginkgo Folium extract  prednisone  Ghrelin-Obestatin signaling pathway  mice

摘要:

目的 研究银杏叶提取物联合泼尼松对慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）小鼠Ghrelin-Obestatin信号通路的影响。方法 40只健康SPF小鼠随机分为5组。空白组不做处理，其余4组均诱导造COPD小鼠模型，在造模第8天开始，3组治疗组分别灌胃银杏叶提取物（0.4 mL·kg^-1·d^-1）、泼尼松（10 mg·kg^-1·d^-1）、联合药物治疗（0.4 mL·kg^-1银杏叶提取物+10 mg·kg^-1泼尼松），空白组、模型组予以生理盐水，连续给药28 d，采用Buxco系统检测小鼠肺功能PIF、PEF、MV后处死小鼠，采血样及肺组织样本。HE染色考察肺组织病理学变化；RT-PCR检测肺组织Ghrelin、GHSR、GPR39 mRNA表达；Western blotting检测肺组织Ghrelin、GHSR、Obestatin、GPR39蛋白含量；ELISA检测血清TNF-α、IL-6、IL-8水平。结果 与模型组相比，不同给药组均减轻COPD小鼠肺组织病理损伤，联合用药组效果最佳；联合用药组肺功能PIF、PEF、MV较模型组明显升高（P<0.05）；联合用药组Ghrelin、GHSR、GPR39 mRNA及蛋白表达较模型组明显升高（P<0.05），Obestatin蛋白表达较模型组明显升高（P<0.05）；仅联合用药组血清TNF-α、IL-6、IL-8含量较模型组明显降低（P<0.05），效果优于单一药物组。结论 银杏叶提取物联合泼尼松可影响Ghrelin-Obestatin信号通路，减轻炎症反应，改善肺功能，且较单一用药效果更佳。

Abstract:

OBJECTIVE To study the effects of Ginkgo Folium extract combined with prednisone on Ghrelin-Obestatin signaling pathway in mice with chronic obstructive pulmonary disease(COPD). METHODS Forty healthy SPF mice were randomly divided into 5 groups, the blank group was not treated, and the other 4 groups of mice were induced with COPD model. On the 8th day of modeling, the three groups were treated with Ginkgo Folium extract(0.4 mL·kg^-1·d^-1), prednisone(10 mg·kg^-1·d^-1) and combination therapy(0.4 mL·kg^-1 Ginkgo Folium extract+10 mg·kg^-1 prednisone), while the blank group and model group were given normal saline. The mice were examined for lung function PIF, PEF and MV using the Buxco system and then the mice were sacrificed after 28 d of continuous administration. Blood samples and lung tissue samples were taken. HE staining was used to investigate the pathological changes of lung tissue; RT-PCR was used to detect the expression of Ghrelin, GHSR and GPR39 mRNA in lung tissue; Western blotting was used to detect the content of Ghrelin, GHSR, Obestatin and GPR39 in lung tissue; serum levels of TNF-α, IL-6 and IL-8 were measured by ELISA. RESULTS Compared with model group, different groups of administration alleviated the pathological damage of lung tissue in COPD mice, and the effect of combination group was the best. The PIF, PEF and MV of pulmonary function in combination group were significantly higher than model group(P<0.05); the mRNA and protein expression of Ghrelin, GHSR and GPR39 in combination group was significantly higher than that in model group(P<0.05), and the expression of Obestatin protein was significantly higher than that in model group(P<0.05); the levels of serum TNF-α, IL-6 and IL-8 in combination group were significantly lower than those in model group(P<0.05), and the effect was better than single drug groups. CONCLUSION Ginkgo Folium extract combined with prednisone can affect the Ghrelin-Obestatin signaling pathway, significantly reduce inflammation and improve lung function and it is better than single drug.