Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan,
Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Pharmacology. 2024;109(2):121-126. doi: 10.1159/000536348. Epub 2024 Feb 12.
The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD.
Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22-24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet.
Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF.
This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.
传统的日本汉方药 hochuekkito（TJ-41）已被报道可改善慢性阻塞性肺疾病（COPD）患者的全身炎症和营养不良。TJ-41 也被认为具有预防流感病毒感染的作用。然而，其在 COPD 急性加重（AECOPD）中的作用仍有待阐明。我们之前的研究建立了一种通过气管内给予猪胰弹性蛋白酶（PPE）和聚肌苷酸-聚胞苷酸[poly（I：C）]诱导的病毒感染相关 AECOPD 的小鼠模型。在这里，我们使用该模型研究了 TJ-41 在 AECOPD 中的作用。
使用无特定病原体的 C57BL/6J 小鼠。通过在第 0 天用 PPE 气管内处理来诱导 COPD 模型。为了生成 AECOPD 的小鼠模型，在 PPE 处理后第 22-24 天用 poly（I：C）气管内给药。在第 25 天处死并分析小鼠。将小鼠喂以含有 2%TJ-41 的饮食或对照饮食。
TJ-41 的每日口服摄入显著减少了支气管肺泡灌洗液（BALF）中的中性粒细胞和淋巴细胞数量，这伴随着全肺匀浆中涉及中性粒细胞迁移的 CXC 趋化因子 Cxcl1 和 Cxcl2 的转录物减少，以及 BALF 中 Cxcl2 浓度降低。
本研究表明 TJ-41 在 AECOPD 小鼠模型中具有抗炎作用，提示 TJ-41 对 COPD 的治疗有效。评估 TJ-41 在 AECOPD 中的治疗疗效的临床研究将具有重要意义。
