Number 2 Feibi Recipe Ameliorates Pulmonary Fibrosis by Inducing Autophagy Through the GSK-3β/mTOR Pathway.

Number 2 Feibi Recipe (N2FBR) is a traditional Chinese medicine formula for treating idiopathic pulmonary fibrosis. N2FBR inhibits H2O2-mediated oxidative stress damage in alveolar epithelial cells by increasing autophagy, as we previously demonstrated. However, it is unknown if similar mechanisms occur in vivo. We established a pulmonary fibrosis model by instilling bleomycin (BLM) from the airway to examine the effects of N2FBR on pulmonary fibrosis and investigate its probable mechanism in this work. We discovered that N2FBR treatment effectively alleviated interstitial fibrosis as well as collagen deposition, primarily in upregulating SOD, GSH-Px, T-AOC and downregulating MDA content. N2FBR also increased the expression of LC3B, Beclin-1, LAMP1, TFEB and downregulated the expression of p62, legumain. N2FBR treatment boosted the production of autophagosomes, according to the results of the TEM observation. Furthermore, we explored that N2FBR exerted its anti-oxidative stress and pro-autophagy effects via GSK-3β/mTOR signalling pathway. Therefore, these results provide further evidence for the protective effect of N2FBR in pulmonary fibrosis. Our findings could have ramifications for the development of antifibrosis therapies.

二号肺痹方（N2FBR）是一种治疗特发性肺纤维化的中药方剂。正如我们之前所证明的，N2FBR通过增强自噬抑制肺泡上皮细胞中过氧化氢介导的氧化应激损伤。然而，尚不清楚在体内是否存在类似机制。在本研究中，我们通过气道滴注博来霉素（BLM）建立肺纤维化模型，以检验N2FBR对肺纤维化的影响并探究其可能的机制。我们发现N2FBR治疗有效地减轻了间质纤维化以及胶原沉积，主要是通过上调超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH - Px）、总抗氧化能力（T - AOC）以及下调丙二醛（MDA）含量。N2FBR还增加了LC3B、Beclin - 1、LAMP1、TFEB的表达，并下调了p62、 legumain的表达。根据透射电镜（TEM）观察结果，N2FBR治疗促进了自噬体的产生。此外，我们探究发现N2FBR通过GSK - 3β/mTOR信号通路发挥其抗氧化应激和促进自噬的作用。因此，这些结果为N2FBR在肺纤维化中的保护作用提供了进一步的证据。我们的研究结果可能对抗纤维化疗法的发展产生影响。