Zhou Ying, Chai Xiujuan
Department of Pneumology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China.
J Cell Biochem. 2020 Jan;121(1):651-660. doi: 10.1002/jcb.29310. Epub 2019 Aug 12.
Idiopathic pulmonary fibrosis (IPF), a chronic, progressive and irreversible disease, needs long-term treatment. Bicyclol was found to play a great role in pulmonary fibrosis, and the present study is to explore how bicyclol affects IPF with the involvement of microRNA-455-3p (miR-455-3p) and Bax. Bleomycin (BLM) was used to induce the IPF model in Sprague-Dawley rats to detect the expression of miR-455-3p, Bax, and B-cell lymphoma factor 2 (Bcl-2). Moreover, to further investigate the mechanisms of bicyclol, the BLM-induced fibrotic cell model was used after the lung epithelial cells HPAEpiC received miR-455-3p knockout treatment. The rats were then treated with vehicle and bicyclol, respectively. The apoptosis of fibrotic cells and Bax/Bcl-2 were identified. Inhibition function of bicyclol was optimal at a dose of 150 mg/kg. Bicyclol inhibited cell apoptosis and reduced Bax/Bcl-2 expression in rats. miR-455-3p could potentially bind to Bax gene. Bicyclol reduced the levels of methylenedioxyamphetamine, superoxide dismutase, and glutathione in rat lung tissue, inhibited the apoptosis of rats with IPF and upregulated miR-455-3p expression. In vitro studies showed that bicyclol significantly promoted miR-455-3p expression in HPAEpiC fibrosis. Bicyclol inhibited fibrosis-induced apoptosis of HPAEpiC in alveolar epithelial cells through promoting miR-455-3p, which inhibited Bax expression in IPF. Bicyclol may suppress the apoptosis of alveolar epithelial cells by upregulating miR-455-3p. This study laid a theoretical foundation for further understanding of IPF and searching for new molecular therapeutic targets.
特发性肺纤维化（IPF）是一种慢性、进行性且不可逆的疾病，需要长期治疗。已发现双环醇在肺纤维化中发挥重要作用，本研究旨在探讨双环醇如何通过微小RNA - 455 - 3p（miR - 455 - 3p）和Bax参与影响IPF。采用博来霉素（BLM）诱导Sprague - Dawley大鼠建立IPF模型，以检测miR - 455 - 3p、Bax和B细胞淋巴瘤因子2（Bcl - 2）的表达。此外，为进一步研究双环醇的作用机制，在肺上皮细胞HPAEpiC接受miR - 455 - 3p敲除处理后，使用BLM诱导的纤维化细胞模型。然后分别用赋形剂和双环醇对大鼠进行治疗。鉴定纤维化细胞的凋亡情况以及Bax/Bcl - 2水平。双环醇在剂量为150mg/kg时抑制作用最佳。双环醇可抑制大鼠细胞凋亡并降低Bax/Bcl - 2表达。miR - 455 - 3p可能与Bax基因潜在结合。双环醇可降低大鼠肺组织中亚甲二氧基苯丙胺、超氧化物歧化酶和谷胱甘肽水平，抑制IPF大鼠的细胞凋亡并上调miR - 455 - 3p表达。体外研究表明，双环醇可显著促进HPAEpiC纤维化中miR - 455 - 3p的表达。双环醇通过促进miR - 455 - 3p抑制肺泡上皮细胞中纤维化诱导的HPAEpiC凋亡，而miR - 455 - 3p可抑制IPF中的Bax表达。双环醇可能通过上调miR - 455 - 3p抑制肺泡上皮细胞凋亡。本研究为进一步了解IPF和寻找新的分子治疗靶点奠定了理论基础。
