Department of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai 201299, China.
Department of Cardiothoracic Surgery, Renji Hospital Shanghai Jiaotong University School of Medicine Affiliated Hospital, Shanghai 200127, China.
J Environ Pathol Toxicol Oncol. 2020;39(4):291-298. doi: 10.1615/JEnvironPatholToxicolOncol.2020035116.
Acute lung injury (ALI) is a severe inflammatory disorder that causes respiratory failure. Cases of ALI are reported with increasing mortality rates each year. In this study, we investigated the anti-inflammatory role of tomentosin and its fundamental mechanisms against lipopolysaccharide (LPS)-induced ALI via the suppression of Toll-like receptor (TLR4)/nuclear factor-kappa beta (NF-κB) pathway in a mouse model of sepsis. ALI was induced to BALB/c mice through the administration of 10 μg of LPS concomitantly with tomentosin (20 and 25 mg/kg) treatment. Dexamethasone was used as a standard drug. Inflammatory cells were measured using a hemocytometer; myeloperoxidase (MPO) enzyme activity and pro-inflammatory cytokines were determined using commercial kits. The lung tissues of animals were examined histologically. The expression level of TLR4/NF-κB signaling molecules were analyzed by Western blotting. Tomentosin treatment decreased lung edema and reduced the levels of macrophages, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Tomentosin also suppressed the status of pro-inflammatory markers and reduced the activation of iNOS, MPO, COX-2, and PGE2 in the lung. Tomentosin appreciably down-regulated the NF-κB/TLR4 signaling pathway in sepsis mice. Histological study also showed the protective effects of tomentosin. These findings show that tomentosin protects the LPS-induced ALI via suppression of TLR4/NF-κB signaling pathway in sepsis mice. Tomentosin could be a promising therapeutic agent to treat sepsis.
急性肺损伤（ALI）是一种严重的炎症性疾病，可导致呼吸衰竭。每年ALI 的报告病例死亡率都在增加。在这项研究中，我们通过抑制 Toll 样受体（TLR4）/核因子-κB（NF-κB）通路，研究了绒毛钩吻素在脂多糖（LPS）诱导的脓毒症小鼠模型中对抗 ALI 的抗炎作用。通过同时给予 LPS（10 μg）和绒毛钩吻素（20 和 25 mg/kg）来诱导 BALB/c 小鼠发生 ALI。地塞米松被用作标准药物。使用血细胞计数器测量炎性细胞；使用商业试剂盒测定髓过氧化物酶（MPO）酶活性和促炎细胞因子。检查动物的肺组织的组织学。通过 Western blot 分析 TLR4/NF-κB 信号分子的表达水平。绒毛钩吻素治疗可减少肺水肿，并降低支气管肺泡灌洗液中巨噬细胞、淋巴细胞和中性粒细胞的水平。绒毛钩吻素还抑制了促炎标志物的状态，并减少了肺中 iNOS、MPO、COX-2 和 PGE2 的激活。绒毛钩吻素可显著下调脓毒症小鼠的 NF-κB/TLR4 信号通路。组织学研究也显示了绒毛钩吻素的保护作用。这些发现表明，绒毛钩吻素通过抑制 TLR4/NF-κB 信号通路来保护 LPS 诱导的 ALI 在脓毒症小鼠中。绒毛钩吻素可能是治疗脓毒症的一种有前途的治疗药物。
