摘要
目的:比较不同时期给予吡非尼酮和尼达尼布对博来霉素诱导的小鼠肺纤维化的作用。方法:根据给药时间和给药时长,建立5类小鼠模型:炎症时期给药模型、纤维化早期预防给药模型、纤维化早期治疗模型、纤维化晚期治疗模型和全程给药模型,分别检测炎症指标和纤维化指标。结果:(1)抗炎抗氧化评估:吡非尼酮和尼达尼布均能降低炎症细胞数目,抑制炎症因子分泌。吡非尼酮对白细胞介素1β(IL-1β)和IL-4的抑制效果较好(P<0.01),尼达尼布对IL-6、IFN-γ的抑制作用较好(P<0.05)。吡非尼酮可显著提高超氧化物歧化酶(SOD)活性(P<0.01),而尼达尼布可显著降低丙二醛(MDA)和髓过氧化物酶(MPO)含量(P<0.01)。(2)肺组织胶原含量检测:在纤维化早期治疗模型、纤维化晚期治疗模型、全程给药模型中,尼达尼布对羟脯氨酸的抑制作用均优于吡非尼酮(P<0.05)。而吡非尼酮在纤维化早期预防给药模型中对羟脯氨酸的抑制作用较好(P<0.01)。(3)肺组织病理学评价:吡非尼酮和尼达尼布均可减少肺组织炎症浸润和纤维化面积,抑制效果对比结果同胶原检测结果一致。结论:在博来霉素诱导的小鼠肺纤维化模型中,吡非尼酮和尼达尼布均具有抗炎、抗氧化及抗肺纤维化作用,其中吡非尼酮在预防给药模型中作用效果更优,尼达尼布在早期、晚期和全程治疗模型中作用效果更优。
AIM:To compare the effects of pirfenidone and nintedanib on bleomycin-induced mice pulmonary fibrosis model in different periods.METHODS:Five mice models were established according to the schedule of drug administration:a inflammatory phase model and 4 fibrotic phase models including the early prevention study group,early therapy study group,late therapy study group and full-course therapy study group.The indicators of lung inflammatory and lung fibrosis were detected respectively.RESULTS:(1)The level of anti-inflammatory and antioxidant indicators:both pirfenidone and nintedanib reduced the number of inflammatory cells and inhibited the secretion of inflammatory factors.Pirfenidone had a better effect on inhibition of interleukin(IL)-1βand IL-4(P<0.01),while nintedanib had a better effect on inhibition of IL-6 and IFN-γ(P<0.05).Pirfenidone significantly increased superoxide dismutase(SOD)activity(P<0.01),and nintedanib significantly reduced malondialdehyde(MDA)and myeloperoxidase(MPO)levels(P<0.01).(2)Collagen content in lung tissue:the inhibitory effect of nintedanib on hydroxyproline content in mouse lung was better than that of pirfenidone in the early therapy study group,late therapy study group and full-course therapy study group of the fibrotic phase models(P<0.05).Pirfenidone had a better inhibitory effect on hydroxyproline content than nintedanib in the early prevention study group(P<0.01).(3)Pathological evaluation of lung tissue:both pirfenidone and nintedanib reduced the inflammatory infiltration and fibrotic area of the lung tissues.The inhibition trend was consistent with that of collagen content.CONCLUSION:Both pirfenidone and nintedanib have anti-inflammatory,anti-oxidative and anti-fibrosis effects in bleomycin-induced pulmonary fibrosis in mice.Pirfenidone is more effective in the early prevention study group,and nintedanib has a better effect in early therapy study group,late therapy study group and full-course therapy study group.
作者
吕紫薇
黄凯
甘文华
高劭妍
杨波
赫连凯玥
李霄鹤
周红刚
LV Zi-wei;HUANG Kai;GAN Wen-hua;GAO Shao-yan;YANG Bo;HELIAN Kai-yue;LI Xiao-he;ZHOU Hong-gang(State Key Laboratory of Medicinal Chemical Biology,College of Pharmacy and Key Laboratory of Molecular Drug Research,Nankai University,Tianjin 300350,China;High-throughput Molecular Drug Screening Centre,Tianjin International Joint Academy of Biomedicine,Tianjin 300070,China;Department of Thoracic Surgery,Tianjin Fist Center Hospital,Tianjin 300192,China;Australian National University,College of Health and Medicine and College of Science,2601 Canberra,ACT,Australia)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2020年第1期112-118,共7页
Chinese Journal of Pathophysiology
基金
国家重点研发计划(No.2018YFA0507203)
国家重大新药创制科技重大专项(No.SQ2018ZX090201)
南开大学中央高校基本科研业务费专项资金(No.63171601)
南开大学药物化学生物学国家重点实验室开放基金资助项目(No.2018128)
关键词
特发性肺纤维化
吡非尼酮
尼达尼布
炎症
氧化应激
Idiopathic pulmonary fibrosis
Pirfenidone
Nintedanib
Inflammation
Oxidative stress
