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六君子胶囊通过JAK/STAT通路对肺泡上皮细胞及慢性阻塞性肺疾病的影响

Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway.

作者信息

Wang Chengyang, Ding Huanzhang, Tang Xiao, Li Zegeng, Gan Lei

机构信息

Department of Traditional Chinese Medicine, The First Affiliated Hospital, Anhui Medical University, Hefei, China.

Graduate School, Anhui University of Chinese Medicine, Hefei, China.

出版信息

Cell Physiol Biochem. 2017;43(2):743-756. doi: 10.1159/000481558. Epub 2017 Sep 27.

Abstract

BACKGROUND/AIMS: To evaluate the effect of Liuweibuqi capsules on chronic obstructive pulmonary disease (COPD) through the JAK/STAT pathway.

METHODS

Lung function was measured with a spirometer. Changes in lung histology were observed using H&E staining. Cigarette smoke extract combined with lipopolysaccharide (CSE+LPS) was used to establish the cellular COPD model. Cytokine levels were determined using ELISA, and changes in the JAK/STAT pathway were evaluated using western blotting. The CCK8 method and flow cytometry were used to measure cell viability and apoptosis, respectively.

RESULTS

Liuweibuqi capsules reduced the damage in the lung tissues and the loss of lung function in the COPD rats. Additionally, the levels of interleukin (IL)-1β, interferon γ (IFNγ), IL-6, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 were higher, whereas IL-10 was lower in the model control (MC) and CSE+LPS groups than in the normal group. The phosphorylation levels of JAK1, JAK2, STAT1, STAT3 and STAT5 were higher and the levels of SOCS1 and SOCS3 were lower in the MC group and CSE+LPS group compared with the normal group. After Liuweibuqi capsule treatment, the expression of inflammatory cytokines and elements of the JAK/STAT pathway were lower. In addition, over-expression of STAT3 blocked the effects of the Liuweibuqi capsules on the release of inflammatory cytokines, cell viability and apoptosis.

CONCLUSION

Our findings suggested that Liuweibuqi capsule might effectively ameliorate the progression of COPD via the JAK/STAT pathway.

摘要

背景/目的:通过JAK/STAT信号通路评估六君子胶囊对慢性阻塞性肺疾病(COPD)的影响。

方法

使用肺功能仪测量肺功能。采用苏木精-伊红(H&E)染色观察肺组织学变化。用香烟烟雾提取物联合脂多糖(CSE+LPS)建立细胞COPD模型。采用酶联免疫吸附测定(ELISA)法测定细胞因子水平,并用蛋白质免疫印迹法评估JAK/STAT信号通路的变化。分别采用CCK8法和流式细胞术检测细胞活力和凋亡情况。

结果

六君子胶囊减轻了COPD大鼠肺组织的损伤和肺功能的丧失。此外,模型对照组(MC)和CSE+LPS组白细胞介素(IL)-1β、干扰素γ(IFNγ)、IL-6、肿瘤坏死因子(TNF)-α和转化生长因子(TGF)-β1的水平高于正常组,而IL-10水平低于正常组。与正常组相比,MC组和CSE+LPS组JAK1、JAK2、STAT1、STAT3和STAT5的磷酸化水平较高,而SOCS1和SOCS3水平较低。六君子胶囊治疗后,炎症细胞因子的表达和JAK/STAT信号通路的成分降低。此外,STAT3的过表达阻断了六君子胶囊对炎症细胞因子释放、细胞活力和凋亡的影响。

结论

我们的研究结果表明,六君子胶囊可能通过JAK/STAT信号通路有效改善COPD的进展。

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