Guangxi Medical University, Nanning, China; Endoscopy Center of Hunan Chest Hospital, Changsha, China.
Endoscopy Center of Hunan Chest Hospital, Changsha, China.
Life Sci. 2020 Jun 1;250:117552. doi: 10.1016/j.lfs.2020.117552. Epub 2020 Mar 13.
This study aimed to explore the possible mechanism of trauma-induced laryngotracheal stenosis and potential protective and therapeutic efficacy of quercetin on trauma-induced laryngotracheal stenosis.
The expression and activity of fibrotic factors [interleukin (IL)-6, IL-8, autophagy related 5 (ATG5), collagen (COL)-1, tumor growth factor (TGF)-β COL-3, microtubule-associated proteins 1A/1B light chain 3A (LC3), and vascular endothelial growth factor (VEGF)] and fibrotic signaling mediators [mammalian target of rapamycin (mTOR) and phosphorylated AKT (pAKT)] were detected by real-time quantitative PCR (qRT-PCR), ELISA, Western blot, and immunohistochemical staining, respectively, in the lipopolysaccharide (LPS)-induced WI-38 (a human embryonic lung fibroblast cell line) cellular fibrotic model and a trauma-induced rabbit tracheal stenosis model, with and without quercetin treatment.
Pre-treatment with quercetin significantly reversed the LPS-induced upregulation of pro-fibrotic factors (IL-6, IL-8, COL-1, COL-3, LC3) and fibrotic signaling mediators (mTOR and AKT), and it induced the downregulation of ATG5 in the WI-38 cells. Furthermore, the anti-fibrotic activity of quercetin was confirmed in the trauma-induced rabbit tracheal stenosis model. Thus, the nasogastric administration of quercetin attenuated the tracheal stenosis of the rabbit tracheal stenosis model, in addition to effectively reversing an increase in pro-fibrotic factors (VEGF, IL-6, TGF-β, COL-1, and COL-3) and fibrotic signaling mediators (mTOR and AKT), as well as downregulating ATG5 of the rabbit tracheal stenosis model.
Quercetin exhibits anti-fibrotic activity by inhibiting pro-fibrotic factors and AKT/mTOR signaling pathway, in addition to activating autophagy activity. This study provided experimental evidence supporting the application of quercetin in tracheal stenosis, clinically.
本研究旨在探讨创伤性喉气管狭窄的可能机制，以及槲皮素对创伤性喉气管狭窄的潜在保护和治疗作用。
通过实时定量 PCR(qRT-PCR)、酶联免疫吸附试验(ELISA)、Western blot 和免疫组织化学染色，分别检测纤维化因子[白细胞介素(IL)-6、IL-8、自噬相关蛋白 5(ATG5)、胶原蛋白(COL)-1、转化生长因子(TGF)-β、COL-3、微管相关蛋白 1A/1B 轻链 3A(LC3)和血管内皮生长因子(VEGF)]和纤维化信号介质[哺乳动物雷帕霉素靶蛋白(mTOR)和磷酸化 AKT(pAKT)]在脂多糖(LPS)诱导的 WI-38(人胚肺成纤维细胞系)细胞纤维化模型和创伤性兔气管狭窄模型中的表达和活性，以及槲皮素治疗前后的表达和活性。
槲皮素预处理可显著逆转 LPS 诱导的促纤维化因子(IL-6、IL-8、COL-1、COL-3、LC3)和纤维化信号介质(mTOR 和 AKT)的上调，并诱导 WI-38 细胞中 ATG5 的下调。此外，在创伤性兔气管狭窄模型中证实了槲皮素的抗纤维化活性。因此，槲皮素的鼻饲给药减轻了兔气管狭窄模型的气管狭窄，除了有效逆转促纤维化因子(VEGF、IL-6、TGF-β、COL-1 和 COL-3)和纤维化信号介质(mTOR 和 AKT)的增加，还下调了兔气管狭窄模型的 ATG5。
槲皮素通过抑制促纤维化因子和 AKT/mTOR 信号通路，以及激活自噬活性，表现出抗纤维化活性。这项研究为槲皮素在临床上应用于气管狭窄提供了实验依据。
