白术内酯 III 通过激活 Nrf2/NQO1/HO-1 通路减轻博莱霉素诱导的大鼠实验性肺纤维化和氧化应激。
Atractylenolide III attenuates bleomycin-induced experimental pulmonary fibrosis and oxidative stress in rat model via Nrf2/NQO1/HO-1 pathway activation.
机构信息
Department of Pharmacy, Jinan Second People's Hospital, Jinan, Shandong, China.
Department of Pharmacy, Jining No.1 People's Hospital, Jining, Shandong, China.
出版信息
Immunopharmacol Immunotoxicol. 2020 Oct;42(5):436-444. doi: 10.1080/08923973.2020.1806871. Epub 2020 Aug 29.
BACKGROUND
Bleomycin (BLM) is a chemotherapy drug used to treat cancer, one of which side effects is that it can lead to pulmonary fibrosis (PF). Atractylenoide III (AtrIII), derived from the dried roots of of compositae, is one of the main active substances of . It has anti-inflammatory, anti-tumor and other effects. This study aimed to investigate whether AtrIII alleviated BLM-induced PF and oxidative stress in rats through the nuclear factor erythroid-2-related factor 2/NQO1,NAD(P)H:quinine oxidoreductase 1/Heme oxygenase-1 (Nrf2/NQO1/HO-1) pathway.
METHODS
A BLM-induced pulmonary fibrosis model in SD rats was established. The respiratory dynamics were evaluated by using Wholebody flow-through plethysmography. Lung injury and pulmonary fibrosis were observed by Hematoxylin-eosin (HE) and Masson staining. Apoptosis was assay by Tunel assay. Inflammatory factors were detected with commercial kits. Expression of mRNAs and proteins were detected by RT-qPCR and Western blot, respectively.
RESULTS
AtrIII (1.2, 2.4 mg/kg) improved the lung injury and lung function in the BLM-induced Sprague-Dawley (SD) rats. AtrIII reduced the apoptosis rate and protein expression of Caspase-3 and Caspase-9. AtrIII (1.2, 2.4 mg/kg) decrease the pulmonary fibrosis damage and protein expression transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA). AtrIII also down-regulated the levels of interleukin 6 (IL-6), inductible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α), while up-regulated the level of IL-10 in peripheral blood serum. Moreover, AtrIII (1.2, 2.4 mg/kg) increased the activity of superoxide dismutase (SOD) and glutathione (GSH), while decreased the malondialdehyde (MDA) content and lactate dehydrogenase (LDH) activity. AtrIII (1.2, 2.4 mg/kg) increased the levels of Nrf2, NQO1 and HO-1. In addition, AtrIII reversed the effects of Nrf2 interference on pulmonary fibrosis damage, decreased SOD and GSH activity, and increased MDA content.
CONCLUSION
AtrIII could attenuate the pulmonary fibrosis and reliev oxidative stress through the Nrf2/NQO1/ HO-1 pathway.
背景
博来霉素（BLM）是一种用于治疗癌症的化疗药物，其副作用之一是导致肺纤维化（PF）。苍术三醇（AtrIII），源自菊科植物的干燥根，是 的主要活性物质之一。它具有抗炎、抗肿瘤等作用。本研究旨在探讨苍术三醇是否通过核因子红细胞 2 相关因子 2/NQO1、NAD（P）H：醌氧化还原酶 1/血红素加氧酶-1（Nrf2/NQO1/HO-1）通路缓解 BLM 诱导的大鼠 PF 和氧化应激。
方法
建立 SD 大鼠 BLM 诱导的肺纤维化模型。采用全身体外流量描记术评估呼吸动力学。苏木精-伊红（HE）和 Masson 染色观察肺损伤和肺纤维化。Tunel 测定法检测细胞凋亡。采用商业试剂盒检测炎症因子。分别采用 RT-qPCR 和 Western blot 检测 mRNA 和蛋白质的表达。
结果
苍术三醇（1.2、2.4mg/kg）改善 BLM 诱导的 Sprague-Dawley（SD）大鼠的肺损伤和肺功能。苍术三醇降低了细胞凋亡率和 Caspase-3、Caspase-9 的蛋白表达。苍术三醇（1.2、2.4mg/kg）降低了肺纤维化损伤和转化生长因子-β（TGF-β）和α-平滑肌肌动蛋白（α-SMA）的蛋白表达。苍术三醇还下调了外周血血清中白细胞介素 6（IL-6）、诱导型一氧化氮合酶（iNOS）和肿瘤坏死因子-α（TNF-α）的水平，同时上调了白细胞介素 10（IL-10）的水平。此外，苍术三醇（1.2、2.4mg/kg）增加了超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的活性，同时降低了丙二醛（MDA）含量和乳酸脱氢酶（LDH）活性。苍术三醇（1.2、2.4mg/kg）增加了 Nrf2、NQO1 和 HO-1 的水平。此外，苍术三醇逆转了 Nrf2 干扰对肺纤维化损伤的影响，降低了 SOD 和 GSH 的活性，增加了 MDA 的含量。
结论
苍术三醇通过 Nrf2/NQO1/HO-1 通路减轻肺纤维化并缓解氧化应激。
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