白介素11拮抗剂对实验性小鼠肺纤维化的作用  

Effects of interleukin-11 antagonist on pulmonary fibrosis in mice

作　　者：吴礼循 吴翔[2] WU Li-xun;WU Xiang(Department of Clinical Laboratory,Haikou Hospital of the Maternal and Child Health;Department of Clinical Laboratory,Hainan Provincial Hospital of Traditional Chinese Medicine,Haikou 570203,China)

机构地区：[1]海口市妇幼保健院检验科 [2]海南省中医院检验科,海口570203

出　　处：《中国应用生理学杂志》2021年第3期308-312,共5页Chinese Journal of Applied Physiology

摘　　要：目的:观察拮抗白介素11(IL-11)对博来霉素(BLM)诱导的实验性小鼠肺纤维化的作用。方法:将120只雄性C57BL/6小鼠随机分为正常对照组、IL-11拮抗剂组、BLM组和BLM+IL-11拮抗剂组(每组各30只)。BLM组和BLM+IL-11拮抗剂组小鼠一次性气管注射BLM(1.5 mg/kg)诱导肺纤维化。于造模当日开始,IL-11拮抗剂组和BLM+IL-11拮抗剂组小鼠每间隔3 d尾静脉注射IL-11拮抗剂IL-11 RαFC(2.5 mg/kg)。观察各组小鼠生存状态。于造模后第21日取肺组织进行HE染色、Masson染色以及Ashcroft评分评价肺纤维化程度。通过碱水解法测定肺组织中羟脯氨酸(HYP)的含量;采用Real-time PCR和Western blot检测肺组织中Collagen I、Collagen III和α-SMA的基因和蛋白表达;采用酶联免疫吸附法测定肺组织中TGF-β1含量。结果:与正常对照组相比,BLM可降低小鼠存活率(P<0.05),破坏肺组织结构,导致大量胶原沉积,显著升高HYP含量、肺组织中Collagen I、Collagen III和α-SMA的基因和蛋白表达(P<0.05),以及TGF-β1含量(P<0.05)。而IL-11 RαFc处理可改善肺纤维小鼠的生存率,减轻肺组织病理学改变以及胶原沉积,减少肺组织中HYP含量(P<0.05),下调肺组织中Collagen I、Collagen III和α-SMA的基因和蛋白表达(P<0.05),以及TGF-β1含量(P<0.05)。结论:IL-11拮抗剂可减轻BLM诱导的小鼠肺纤维化,为临床治疗肺纤维化提供了新思路。Objective:To investigate the effects of interleukin 11(IL-11)antagonist on bleomycin(BLM)-induced pulmonary fibrosis in mice.Methods:C57BL/6 mice were randomly divided into the control group,IL-11 antagonist group,BLM group,and BLM+IL-11 antagonist group(30 in each group).Mice in the BLM group and BLM+IL-11 antagonist group were injected with BLM at the dose of 1.5 mg/kg to induce pulmonary fibrosis.The IL-11 antagonist IL-11 RαFC(2.5 mg/kg)was administered via the tail vein to the mice in the IL-11 antagonist group and BLM+IL-11 antagonist group every 3 days from the BLM injection.The survival status of the mice was observed.On the 21 st day after modeling,HE staining,Masson staining,and Ashcroft score were used to evaluate the degree of pulmonary fibrosis.The content of hydroxyproline(HYP)in lung tissue was determined by the alkaline hydrolysis method.The gene and protein expressions of Collagen I,Collagen III,andα-SMA in lung tissues were detected by real-time PCR and Western blot,respectively.TGF-β1 content in lung tissue was determined by enzyme-linked immunosorbent assay.Results:Compared with the control group,BLM reduced the survival rate,destructed the lung tissue,and increased the gene and protein expressions of Collagen I,Collagen III,α-SMA,and the content of TGF-β1 in lung tissue.While,IL-11 RαFc treatment improved the survival rate of BLM-induced pulmonary mice,reduced pathological changes,and hydroxyproline content in lung tissue.IL-11 RαFc also reduced Collagen I,Collagen III,andα-SMA mRNA and protein expression in the lungs of BLM-treated mice,as well as TGF-β1 content.Conclusion:The IL-11 antagonist alleviates BLM-induced pulmonary fibrosis in mice,which provides a new idea for the clinical treatment of pulmonary fibrosis.

关 键 词：肺纤维化 白介素11 博来霉素 胶原沉积 小鼠 

分 类 号：R563.9[医药卫生—呼吸系统]