Bu-Shen-Fang-Chuan formula attenuates T-lymphocytes recruitment in the lung of rats with COPD through suppressing CXCL9/CXCL10/CXCL11-CXCR3 axis
Bu-Shen-Fang-Chuan formula attenuates T-lymphocytes recruitment in the lung of rats with COPD through suppressing CXCL9/CXCL10/CXCL11-CXCR3 axis
复制标题
补肾防喘方通过抑制CXCL9/CXCL10/CXCL11-CXCR3轴来减少COPD大鼠肺内T淋巴细胞的募集
DOI：
10.1016/j.biopha.2019.109735
复制
发表时间：
2020-03-01
影响因子：
7.5
通讯作者：
Wu, Jinfeng
中科院分区：
文献类型：
--
作者：
Li, Qiuping;Sun, Jing;Wu, Jinfeng
慢性阻塞性肺疾病（COPD）是一种以不可逆气流受限为特征的常见呼吸系统疾病。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），一种中药配方，显着减少COPD急性加重的频率和延迟肺功能下降。然而，其潜在机制仍不清楚。本研究通过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）能有效改善CS引起的肺功能下降，并显著降低支气管肺泡灌洗液（BALF）中的炎性细胞数量。重要的是，BSFCF治疗显著防止了COPD大鼠肺中T淋巴细胞（特别是CD 8（+）T细胞）的积聚。肺组织RNA测序分析表明，BSFCF显著抑制CS染毒大鼠肺组织CXCL 9/CXCL 10/CXCL 11-CXCR 3趋化因子轴。Real-time PCR结果显示，BSFCF能明显抑制CXCL 9、CXCL 10、CXCL 11和CXCR 3的mRNA表达。BSFCF可明显改善CS染毒大鼠肺功能，抑制CD 8（+）T细胞在肺内的聚集，其机制可能与抑制CXCL 9/CXCL 10/CXCL 11-CXCR 3轴有关。
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.