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补肺防喘方通过抑制 CXCL9/CXCL10/CXCL11-CXCR3 轴减少 COPD 大鼠肺内 T 淋巴细胞募集。

Bu-Shen-Fang-Chuan formula attenuates T-lymphocytes recruitment in the lung of rats with COPD through suppressing CXCL9/CXCL10/CXCL11-CXCR3 axis.

机构信息

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China.

Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China; Institutes of Integrative Medicine, Fudan University, Shanghai, 200040, China.

出版信息

Biomed Pharmacother. 2020 Mar;123:109735. doi: 10.1016/j.biopha.2019.109735. Epub 2019 Dec 18.

Abstract

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease characterized by irreversible airflow limitation. The current medications show limited effects on the decline of pulmonary function in COPD. Our multicenter clinical trial found that Bu-Shen-Fang-Chuan fomula (BSFCF), a Chinese herbal formula, markedly reduced the frequencies of acute exacerbation of COPD and delayed lung function decline. However, the underlying mechanisms are still unclear. In this study, we established a COPD rat model through a 6-month exposure to cigarette smoke (CS) and found that BSFCF (7.2 g/kg) effectively improved CS-induced reduction in pulmonary function and remarkably decreased the numbers of inflammatory cells in bronchoalveolar lavage fluid (BALF). Importantly, BSFCF treatment notably prevented the accumulation of T-lymphocytes (especially CD8 T-cells) in the lung of COPD rats. RNA sequencing analysis of lung tissue demonstrated that CXCL9/CXCL10/CXCL11-CXCR3 chemokine axis in the lung of CS-exposed rats was significantly suppressed by BSFCF. Moreover, our Real-time PCR data verified that BSFCF evidently inhibited the mRNA expressions of CXCL9, CXCL10, CXCL11 and CXCR3. Conclusively, BSFCF markedly improved pulmonary function and attenuated CD8 T-cells recruitment in the lung of CS-exposed rats, which were partially through inhibition of CXCL9/CXCL10/CXCL11-CXCR3 axis.

摘要

慢性阻塞性肺疾病(COPD)是一种常见的呼吸系统疾病,其特征是气流不可逆受限。目前的药物对 COPD 患者肺功能下降的影响有限。我们的多中心临床试验发现,补肾防喘方(BSFCF)显著降低了 COPD 急性加重的频率,延缓了肺功能下降。然而,其潜在机制尚不清楚。在这项研究中,我们通过 6 个月的香烟烟雾(CS)暴露建立了 COPD 大鼠模型,发现 BSFCF(7.2g/kg)有效改善了 CS 引起的肺功能下降,并显著减少了支气管肺泡灌洗液(BALF)中的炎症细胞数量。重要的是,BSFCF 治疗明显阻止了 COPD 大鼠肺中 T 淋巴细胞(尤其是 CD8 T 细胞)的积累。肺组织的 RNA 测序分析表明,BSFCF 显著抑制了 CS 暴露大鼠肺中 CXCL9/CXCL10/CXCL11-CXCR3 趋化因子轴的表达。此外,我们的 Real-time PCR 数据验证了 BSFCF 明显抑制了 CXCL9、CXCL10、CXCL11 和 CXCR3 的 mRNA 表达。总之,BSFCF 显著改善了 CS 暴露大鼠的肺功能,减轻了肺中 CD8 T 细胞的募集,部分是通过抑制 CXCL9/CXCL10/CXCL11-CXCR3 轴。

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