College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.
Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2022 Jun 1;17:1285-1298. doi: 10.2147/COPD.S359428. eCollection 2022.
Bufei Jianpi formula (BJF), a traditional Chinese medicine, is an effective and safe therapeutic formula for chronic obstructive pulmonary disease (COPD). BJF treatment is known to reduce the incidence of loose stools in rats with COPD. It is unclear whether BJF regulates gut microbiota. This study examined whether BJF improved mucosal immune function by remodeling the gut microbiota and modulating metabolites in COPD rats.
Sixty Sprague Dawley (SD) rats were randomized into control, model, BJF, aminophylline (APL), and probiotics (PBT) groups. The stable COPD rat model was duplicated using repeated cigarette smoke inhalation and lipopolysaccharide (LPS) injection. Normal saline, BJF, APL, or PBT were intragastrically administered from weeks eight to twelve, and then the rats were sacrificed at week thirteen. Lung and colon tissues were removed; feces were collected. Pulmonary function, histopathology, levels of inflammatory factors, and activation of NF-κB in the lung tissues were evaluated. Gut microbiota were analyzed using 16S rRNA gene sequencing; fecal short-chain fatty acid (SCFA) concentrations were determined using gas chromatography/mass spectrometry. Mucosal immune response-related genes and proteins were determined using quantitative polymerase chain reaction and Western blotting.
BJF improved pulmonary function and reduced lung inflammation. Further, BJF treatment altered the gut microbiota composition and significantly increased the abundance of Firmicutes and the ratio of Firmicutes to Bacteroides, raising SCFA levels, including acetate, butyrate, and propionate levels. However, the abundance of Bacteroidetes, Proteobacteria, Spirochaetes, Clostridiaceae, and Treponema decreased after BJF administration. BJF decreased the gene and protein expression of NLRP3, Caspase-1, IL-8, and IL-1β, and increased GPR43 expression.
Overall, BJF administration improved mucosal immune function by remodeling the gut microbiota and suppressing the SCFAs/GPR43/NLRP3 pathway in COPD rats. This study provides evidence for the mechanisms underlying BJF-induced improvements in COPD and supports clinical application of BJF.
补肺健脾方（BJF）是一种治疗慢性阻塞性肺疾病（COPD）的有效且安全的中药。已知 BJF 治疗可降低 COPD 大鼠的稀便发生率。但尚不清楚 BJF 是否调节肠道微生物群。本研究通过研究 BJF 是否通过重塑肠道微生物群和调节 COPD 大鼠代谢产物来改善黏膜免疫功能。
将 60 只 Sprague Dawley（SD）大鼠随机分为对照组、模型组、BJF 组、氨茶碱（APL）组和益生菌（PBT）组。采用重复香烟烟雾吸入和脂多糖（LPS）注射法复制稳定的 COPD 大鼠模型。从第 8 周到第 12 周，给予生理盐水、BJF、APL 或 PBT 灌胃，第 13 周处死大鼠。取肺和结肠组织；收集粪便。评估肺功能、组织病理学、肺组织中炎症因子水平和 NF-κB 激活情况。采用 16S rRNA 基因测序分析肠道微生物群；采用气相色谱/质谱法测定粪便短链脂肪酸（SCFA）浓度。采用定量聚合酶链反应和 Western 印迹法测定黏膜免疫反应相关基因和蛋白。
BJF 改善了肺功能，减轻了肺部炎症。此外，BJF 治疗改变了肠道微生物群的组成，显著增加了厚壁菌门的丰度和厚壁菌门与拟杆菌门的比例，提高了乙酸盐、丁酸盐和丙酸盐等 SCFA 水平。然而，BJF 给药后，拟杆菌门、变形菌门、螺旋体门、梭菌科和密螺旋体的丰度降低。BJF 降低了 NLRP3、Caspase-1、IL-8 和 IL-1β的基因和蛋白表达，增加了 GPR43 的表达。
总之，BJF 给药通过重塑肠道微生物群和抑制 COPD 大鼠的 SCFAs/GPR43/NLRP3 通路来改善黏膜免疫功能。本研究为 BJF 改善 COPD 的机制提供了证据，并支持 BJF 的临床应用。
