摘要
目的 研究海洋来源天然生物碱类小分子CH103抗PM2.5诱导肺上皮细胞氧化应激和小鼠肺组织炎症损伤的治疗作用及其药理机制。方法 首先建立一定浓度PM2.5诱导II型肺泡上皮细胞A549氧化应激模型,通过MTT、蛋白印迹法等方法检测不同浓度CH103对肺上皮细胞的保护和抗氧化应激作用。然后采用气道滴注PM2.5溶液构建肺部损伤的小鼠模型,通过血象分析仪检测小鼠肺泡灌洗液(BALF)中炎症细胞的数量,酶联免疫吸附法(ELISA)检测BALF上清中细胞因子的含量,通过H&E染色方法对CH103改善PM2.5诱发肺损伤的药物效果进行评价。结果 CH103能够有效抑制PM2.5诱导肺上皮细胞的活力下降和活性氧(ROS)产生,且具有毒性低的优点。同时,CH103显著降低PM2.5诱导肺上皮细胞p38MAPK和NF-κB的磷酸化,明显改善PM2.5诱导小鼠体质量降低的状况,有效减少小鼠BALF中的TNF-α、MCP-1和MMP-13、MMP-14等炎症相关因子以及炎症细胞的水平,并明显改善肺组织病理进展。结论 CH103能够通过p38MAPK和NF-κB信号通路遏制肺上皮细胞氧化损伤和小鼠肺组织炎症浸润、肺泡萎陷、结缔组织增生等病理损伤,可作为治疗肺损伤和预防肺癌性病变的候选化合物用于进一步研究。
Objective To investigate the therapeutic effect and mechanism of CH103 on PM2.5-induced pulmonary dysfunction in mice and cell models.Methods Firstly,The A549 cells were stimulated by PM2.5,the assays including MTT and western blotting were used to test the improvement of different CH103concentrations on the cell model.Secondly,the animal model of pulmonary dysfunction was established by instilling PM2.5 solution into the mice pulmonary cavity,the Leukocyte(White blood cell) and lymphocytes number in bronchoalveolar lavage fluid(BALF) of mice were counted by hemogram analyzer,and the inflammatory cytokines in the supernatant of BALF was analyzed by ELISA assay.Then,phosphorylation levels of NF-κB and p38MAPK in A549 were measured by western blotting.And the effect of CH103on pulmonary damage was evaluated by H&E staining methods.Results The results showed that CH103could significantly improve the lung dysfunction of mice,effectively reduce the contents of inflammatory cytokines such as,TNF-α,MCP-1,MMP-13 and MMP-14 in the supernatant of mice alveolar lavage fluid,and dramatically inhibit the levels of p38MAPK and NF-κB as well as ROS in lung epithelial cell A549.The inflammatory infiltration,alveolar atrophy,ECM deposition and blood vessel congestion in mice lung tissue were obviously improved.Conclusion CH103 could inhibit the oxidative damage in lung epithelial cells,and pathological injury of inflammatory infiltration,alveolar collapse and connective tissue hyperplasia in mice lung tissue through p38MAPK and NF-κB signaling pathways,so it could be used as a candidate compound for the treatment of lung injury and the prevention of lung cancer for further study.
作者
李涛
丛明慧
孙静
田莹莹
LI Tao;CONG Minghui;SUN Jing;TIAN Yingying(Oncology Department,Central Hospital of Linfen City,Linfen 041000,China;Radiotherapy Department,Qingdao Central Hospital,University of Health and Rehabilitation Sciences,Qingdao 266042,China)
出处
《中国海洋药物》
CAS
CSCD
2024年第5期28-36,共9页
Chinese Journal of Marine Drugs
基金
青岛市卫建委科技立项项目(2011-WSZD072)资助。
关键词
海洋生物碱类化合物
氧化应激
肺腔灌洗液
炎症因子
肺泡
marine alkaloid compounds
oxidative stress
pulmonary lavage fluid
inflammatory factors
lung alveolar
