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 rhizoma atractylodis of compositae, is one of the main active substances of rhizoma atractylodis. 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.

中文翻译：

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白术内酯III通过Nrf2 / NQO1 / HO-1途径激活减弱博莱霉素诱导的大鼠实验性肺纤维化和氧化应激。

背景

博来霉素（BLM）是一种用于治疗癌症的化学疗法药物，其副作用之一是可以导致肺纤维化（PF）。苍术内酯III（AtrIII）中，从干燥根衍生苍术菊科植物的，是主要活性物质之一苍术。它具有抗炎，抗肿瘤等作用。这项研究旨在探讨AtrIII是否通过核因子红系2相关因子2 / NQO1，NAD（P）H：奎宁氧化还原酶1 /血红素加氧酶-1（Nrf2 / NQO1 /）减轻大鼠BLM诱导的PF和氧化应激。 HO-1）途径。

方法

建立了BLM诱导的SD大鼠肺纤维化模型。通过使用全身流式体积描记法评估呼吸动力学。苏木-伊红（HE）和Masson染色观察到肺损伤和肺纤维化。通过Tunel测定法测定细胞凋亡。使用商业试剂盒检测到炎症因素。通过RT-qPCR和蛋白质印迹分别检测mRNA和蛋白质的表达。

结果

AtrIII（1.2，2.4 mg / kg）改善了BLM诱导的Sprague-Dawley（SD）大鼠的肺损伤和肺功能。AtrIII降低了Caspase-3和Caspase-9的凋亡率和蛋白表达。AtrIII（1.2，2.4 mg / kg）减少肺纤维化损害和蛋白质表达转化生长因子-β（TGF-β）和α-平滑肌肌动蛋白（α-SMA）。AtrIII还下调了白细胞介素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，同时上调了外周血血清IL-10的水平。此外，AtrIII（1.2，2.4 mg / 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。AtrIII（1.2，2.4 mg / kg）增加Nrf2，NQO1和HO-1的水平。此外，

结论

AtrIII可通过Nrf2 / NQO1 / HO-1途径减轻肺纤维化并缓解氧化应激。