Chelerythrine (CHE) is a natural benzophenanthridine alkaloid, which has shown its anti-fibrosis activity in kidney and liver, while the impact of CHE in pulmonary fibrosis is still unclear. This study is developed to explore the impact and mechanism of CHE in pulmonary fibrosis. Pulmonary fibrosis mouse models were established through intratracheal injection of bleomycin (BLM), after which the mice were intraperitoneally injected with CHE (0.375 or 0.75 mg/kg/d) every other day. The mice were sacrificed at the 28th day to collect blood serum, bronchoalveolar lavage fluid (BALF), and pulmonary tissues. Then, the severity of pulmonary fibrosis and the expression of nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2) in the pulmonary tissues were detected. Western blot analysis quantified the expressions of fibronectin and alpha-smooth muscle actin (α-SMA). The levels of 4-hydroxynonenal (4-HNE), glutathione (GSH), superoxide dismutase (SOD), TGF-β and hydroxyproline (HP) in the BALF, and pulmonary tissues were measured. The expression levels of Nrf2 and its downstream genes, hemeoxygenase-1 (HO-1) and NAD (P) H: quinone oxidoreductase (NQO1) were examined. CHE at the concentration of 0.375 or 0.75 mg/kg/d could attenuate pulmonary fibrosis. CHE injection reduced the expression levels of fibronectin, α-SMA, and TGF-β, upregulated the levels of SOD and GSH and decreased the levels of 4-HNE and HP. Also, CHE increased the expressions of Nrf2, HO-1, and NQO1. Treatment of Nrf2/antioxidant response element (ARE) inhibitor could block the Nrf2/ARE signaling pathway, thus perturbing the inhibition of CHE on BLM-stimulated pulmonary fibrosis in mice. CHE alleviates BLM-induced pulmonary fibrosis in mice through activating the Nrf2/ARE pathway to increase the activity of antioxidant enzymes.

Chelerythrine (CHE) 是一种天然的苯并菲啶类生物碱，已在肾脏和肝脏中显示出其抗纤维化活性，而 CHE 在肺纤维化中的影响尚不清楚。本研究旨在探讨 CHE 在肺纤维化中的影响和机制。通过气管内注射博来霉素（BLM）建立肺纤维化小鼠模型，然后每隔一天腹腔注射CHE（0.375或0.75mg / kg / d）。在第 28 天处死小鼠以收集血清、支气管肺泡灌洗液 (BALF) 和肺组织。然后，检测肺纤维化的严重程度和肺组织中核因子红细胞 2 [NF-E2] 相关因子 2 (Nrf2) 的表达。蛋白质印迹分析量化了纤连蛋白和α-平滑肌肌动蛋白（α-SMA）的表达。测量了 BALF 和肺组织中 4-羟基壬烯醛 (4-HNE)、谷胱甘肽 (GSH)、超氧化物歧化酶 (SOD)、TGF-β 和羟脯氨酸 (HP) 的水平。检查了 Nrf2 及其下游基因 hemeoxygenase-1 (HO-1) 和 NAD (P) H: 醌氧化还原酶 (NQO1) 的表达水平。浓度为 0.375 或 0.75 mg/kg/d 的 CHE 可减轻肺纤维化。CHE注射降低了纤连蛋白、α-SMA和TGF-β的表达水平，上调了SOD和GSH的水平，降低了4-HNE和HP的水平。此外，CHE 增加了 Nrf2、HO-1 和 NQO1 的表达。Nrf2/抗氧化反应元件（ARE）抑制剂的治疗可以阻断 Nrf2/ARE 信号通路，因此扰乱了 CHE 对 BLM 刺激的小鼠肺纤维化的抑制作用。CHE 通过激活 Nrf2/ARE 通路来增加抗氧化酶的活性，从而减轻 BLM 诱导的小鼠肺纤维化。