Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, China; School of Graduates, Beijing University of Chinese Medicine, Beijing, 100029, China.
Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, China.
J Ethnopharmacol. 2024 Jan 10;318(Pt A):116873. doi: 10.1016/j.jep.2023.116873. Epub 2023 Jul 5.
Several children with pneumonia (especially severe cases) have symptoms of cough and expectoration during the recovery stage after standard symptomatic treatment, which eventually results in chronic lung injury. Danggui yifei Decoction (DGYFD), a traditional Chinese formula, has shown clinical promise for the treatment of chronic lung injury during the recovery stage of pneumonia, however, its mechanism of action is yet to be deciphered.
To investigate the therapeutic mechanism of DGYFD for the treatment of chronic lung injury by integrating network pharmacology and transcriptomics.
BALB/c mice were used to establish the chronic lung injury mouse model by intratracheal instillation of lipopolysaccharide (LPS). Pathological analysis of lung tissue, lung injury histological score, lung index, protein levels in bronchoalveolar lavage fluid (BALF), immunohistochemical staining, blood rheology, inflammatory cytokines, and oxidative stress levels were used to evaluate the pharmacological effects of DGYFD. Chemical components of DGYFD were identified using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Integrated network pharmacology together with transcriptomics was used to predict potential biological targets. Western blot analysis was used to verify the results.
In this study, we demonstrated that DGYFD could improve lung injury pathological changes, decreases lung index, down-regulate NO and IL-6 levels, and regulate blood rheology. In addition, DGYFD was able to reduce the protein levels in BALF, up-regulate the expression levels of occludin and ZO-1, improve the ultrastructure of lung tissues, and reverse the imbalance of AT I and AT II cells to repair the alveolar-capillary permeability barrier. Twenty-nine active ingredients of DGYFD and 389 potential targets were identified by UPLC-MS/MS and network pharmacology, and 64 differentially expressed genes (DEGs) were identified using transcriptomics. GO and KEGG analysis revealed that the MAPK pathway may be the molecular target. Further, we found that DGYFD inhibits phosphorylation levels of p38 MAPK and JNK in chronic lung injury mouse models.
DGYFD could regulate the imbalance between the excessive release of inflammatory cytokines and oxidative stress, repair the alveolar-capillary permeability barrier and improve the pathological changes during chronic lung injury by regulating the MAPK signaling pathway.
一些患有肺炎的儿童（特别是重症病例）在接受标准对症治疗后康复阶段会出现咳嗽和咳痰症状，最终导致慢性肺损伤。当归益肺汤（DGYFD）是一种传统的中药配方，已显示出在肺炎康复阶段治疗慢性肺损伤的临床潜力，但作用机制尚待破译。
通过整合网络药理学和转录组学，研究 DGYFD 治疗慢性肺损伤的治疗机制。
采用气管内滴注脂多糖（LPS）的方法建立 BALB/c 小鼠慢性肺损伤模型。通过肺组织病理分析、肺损伤组织学评分、肺指数、支气管肺泡灌洗液（BALF）中蛋白水平、免疫组织化学染色、血液流变学、炎症细胞因子和氧化应激水平评估 DGYFD 的药效。采用超高效液相色谱-串联质谱法（UPLC-MS/MS）鉴定 DGYFD 的化学成分。整合网络药理学与转录组学预测潜在的生物学靶点。采用 Western blot 分析验证结果。
本研究表明，DGYFD 可改善肺损伤的病理变化，降低肺指数，下调 NO 和 IL-6 水平，调节血液流变学。此外，DGYFD 还能降低 BALF 中蛋白水平，上调 occludin 和 ZO-1 的表达水平，改善肺组织超微结构，逆转 AT I 和 AT II 细胞失衡，修复肺泡-毛细血管通透性屏障。通过 UPLC-MS/MS 和网络药理学鉴定出 DGYFD 的 29 种活性成分和 389 个潜在靶点，并通过转录组学鉴定出 64 个差异表达基因（DEGs）。GO 和 KEGG 分析表明 MAPK 通路可能是其分子靶点。进一步研究发现，DGYFD 抑制慢性肺损伤小鼠模型中 p38 MAPK 和 JNK 的磷酸化水平。
DGYFD 通过调节 MAPK 信号通路，可调节炎症细胞因子过度释放与氧化应激失衡，修复肺泡-毛细血管通透性屏障，改善慢性肺损伤的病理变化。
