Zhang Xue, Huang Haidi, Zhang Guanghua, Li Defang, Wang Hongbo, Jiang Wanglin
School of Pharmacy, Binzhou Medical University, Yantai, China.
School of Pharmacy, Yantai University, Yantai, China.
Front Pharmacol. 2019 Aug 20;10:903. doi: 10.3389/fphar.2019.00903. eCollection 2019.
Raltegravir, an inhibitor of human immunodeficiency virus-1 (HIV-1) integrase, has been used to treat HIV/acquired immunodeficiency syndrome; however, its therapeutic effects on pulmonary fibrosis have not been investigated. In this study, the effects of raltegravir (RAV) on transforming growth factor beta 1 (TGF-β1)-induced pulmonary fibrosis on L929 mouse fibroblasts were investigated. In addition, the effects of RAV on an pulmonary fibrosis model induced by intratracheal instillation of bleomycin were investigated. The proliferation of L929 cells was inhibited after RAV treatment. Meanwhile, the and protein expression of nucleotide-binding oligomerization domain-like receptor 3 (NLRP3), high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), prolyl hydroxylase domain protein 2, phosphorylated nuclear factor-κB (p-NF-κB), hypoxia-inducible factor-1α (HIF-1α), collagens I and III was reduced relative to TGF-β1 or the bleomycin group. Raltegravir ameliorated pulmonary fibrosis by reducing the pathology score, collagen deposition, and expression of α-smooth muscle actin, NLRP3, HMGB1, TLR4, inhibitor of kappa B, p-NF-κB, HIF-1α, collagen I, and collagen III. The results of this study demonstrate that RAV attenuated experimental attenuates pulmonary fibrosis by inhibiting NLRP3 activation.
拉替拉韦是一种人类免疫缺陷病毒1型（HIV-1）整合酶抑制剂，已被用于治疗HIV/获得性免疫缺陷综合征；然而，其对肺纤维化的治疗效果尚未得到研究。在本研究中，研究了拉替拉韦（RAV）对转化生长因子β1（TGF-β1）诱导的L929小鼠成纤维细胞肺纤维化的影响。此外，还研究了RAV对博来霉素气管内滴注诱导的肺纤维化模型的影响。RAV处理后，L929细胞的增殖受到抑制。同时，与TGF-β1组或博来霉素组相比，核苷酸结合寡聚化结构域样受体3（NLRP3）、高迁移率族蛋白B1（HMGB1）、Toll样受体4（TLR4）、脯氨酰羟化酶结构域蛋白2、磷酸化核因子κB（p-NF-κB）、缺氧诱导因子-1α（HIF-1α）、胶原蛋白I和III的蛋白表达降低。拉替拉韦通过降低病理评分、胶原沉积以及α平滑肌肌动蛋白、NLRP3、HMGB1、TLR4、κB抑制蛋白、p-NF-κB、HIF-1α、胶原蛋白I和胶原蛋白III的表达来改善肺纤维化。本研究结果表明，RAV通过抑制NLRP3激活减轻实验性肺纤维化。
