气管滴注PM_(2.5)混悬液对肺纤维化小鼠的影响及新对叶百部碱的干预作用  

Effect of intratracheal instillation of PM_(2.5) suspensionon pulmonary fibrosis in mice and the intervention of neotuberostemonine

作　　者：钱秀惠 孙静 付三 汤小艳 许翔鸿[1] 张勉[1] QIAN Xiuhui;SUN Jing;FU San;TANG Xiaoyan;XU Xianghong;ZHANG Mian(School of Traditional Chinese Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学中药学院,南京211198

出　　处：《中国药科大学学报》2021年第4期455-462,共8页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.81873075);江苏省研究生科研与实践创新计划资助项目(No.KYCX19_0656)。

摘　　要：为了研究PM_(2.5)混悬液对博来霉素(BLM)诱导的肺纤维化小鼠的影响以及新对叶百部碱(NTS)的干预作用,本实验采用析因实验设计研究了PM_(2.5)混悬液给药次数(每周1次或2次)和BLM剂量(1.5、3.0 U/kg)对小鼠肺纤维化模型的影响。小鼠于第0天经气管滴注1.5或3.0 U/kg的BLM;从第1天开始,小鼠每周1次或2次气管滴注5 mg/kg的PM_(2.5)混悬液;从第8天开始,给药组小鼠每天1次灌胃给予30 mg/kg的NTS直至21 d;21 d后观察肺组织病理切片的苏木精-伊红(HE)染色和Masson染色结果,计算小鼠肺系数、肺组织羟脯胺酸(HYP)含量和基于病理切片的HE炎性评分和胶原容积分数(CVF)。结果显示,对于单独滴注PM_(2.5)混悬液的小鼠,每周1次时只有HE炎性评分显著升高,每周2次时HYP和HE炎性评分增加但CVF无显著升高;而PM_(2.5)与BLM联合滴注的各组小鼠的CVF均显著增加;新对叶百部碱能够显著改善联合滴注小鼠的肺组织病理改变、减少胶原沉积,降低小鼠的CVF和α-SMA蛋白的表达,具有抑制肺纤维化的作用。本研究结果表明,单独滴注PM_(2.5)主要引起肺部炎症,即使多次给药引起肺纤维化的可能性也较小;但PM_(2.5)与BLM联合滴注则小鼠肺组织胶原沉积显著增加,大大加重了BLM引起的肺纤维化,提示PM_(2.5)对有呼吸系统疾病或基础性疾病的患者影响很大,而新对叶百部碱对联合滴注模型小鼠的肺纤维化具有明显的改善作用。To investigate the effects of intratracheal instillation of PM_(2.5) suspension on bleomycin(BLM)-induced pulmonary fibrosis in mice and the intervention of neotuberostemonine(NTS),the BLM dose(1.5 or 3.0 U/kg)and PM_(2.5) frequency(1 or 2 times per week)were studied by factorial experiment design.After intratracheal instillation of BLM(1.5 or 3.0 U/kg)on day 0,PM_(2.5)(5 mg/kg)was intratracheally injected to mice once or twice a week from day 1 to day 21,and the mice in the treatment group were given 30 mg/kg NTS by gavage once a day from day 8 to day 21.The degree of pulmonary fibrosis was evaluated by lung coefficient,hydroxyproline(HYP)content,HE staining and Masson staining lung sections as well as their semi-quantitative index(HE inflammatory score and collagen volume fraction,CVF).The results showed that the HE scores increased significantly in mice singly given PM_(2.5) once a week,the HYP content and HE score increased in mice singly given PM_(2.5) twice a week,but their CVF values did not significantly increase.However,the CVF values increased significantly in mice treated with PM_(2.5) and BLM co-infusion.These results suggested that PM_(2.5)(administered singly)could significantly increase BLM-induced collagen deposition and greatly aggravate pulmonary fibrosis although it mainly caused pulmonary inflammation rather than pulmonary fibrosis.NTS could significantly reduce the CVF value andα-SMA protein level of the model mice.It can be concluded that PM_(2.5) has great influence on patients with respiratory diseases,while NTS can improve pulmonary fibrosis induced by the combination of PM_(2.5) and BLM.

关 键 词：PM_(2.5) 博来霉素 混悬液 气管滴注 肺纤维化 新对叶百部碱 

分 类 号：R965[医药卫生—药理学]