摘要
目的:探究乌司他丁在慢性阻塞性肺疾病大鼠模型肺损伤中的保护机制,为治疗慢性阻塞性肺疾病用药提供依据.方法:将大鼠随机分为正常对照组,模型对照组,乌司他丁实验组(n=10).除正常对照组外,所有大鼠均采用烟熏加气管滴注脂多糖复合造模的方法建立慢性阻塞性肺疾病大鼠模型.正常对照组和模型常规治疗组均给予正常生理盐水,实验组给予乌司他丁.观察症状、体征及肺组织学变化并且测定肺功能.采用酶联免疫法检测血清细胞因子的变化,免疫组织化学法、RT-PCR及western blot分别检测JAK/STAT通路、MMP-9及基质金属蛋白酶抑制剂1(MMPs inhibitor1,TIMP1)的表达变化.结果:与正常对照组相比,模型对照组大鼠肺组织受损,肺功能降低.此外,白细胞介素-1β、干扰素γ和IL-6的含量模型对照组高于正常对照组,而IL-4和IL-10模型对照组低于正常对照组.肺组织中JAK1、STAT3、p-STAT3和MMP-9的mRNA和蛋白水平模型对照组高于正常对照组,而TIMP1的mRNA和蛋白水平模型对照组低于正常对照组.治疗后,与模型对照组相比,实验组炎性细胞因子的表达降低,JAK/STAT信号通路、基质金属蛋白酶的表达降低.与模型对照组相比,实验组大鼠肺功能较好,JAK1、STAT3和pSTAT3蛋白表达降低,而TIMP1在实验组的表达升高.结论:乌司他丁可能通过调节JAK1/STAT3通路与MMP9/TIMP1表达改善慢性阻塞性肺疾病的症状.
Aim：To observe effect of ulinastatin on the janus kinase （JAK）/signal transducer and ac-tivator of transcription （STAT）pathway and matrix metallo-proteinases （MMPs）in chronic obstructive pulmonary disease （COPD）rat model.Methods：Rats were randomly divided into a normal group,mod-el group,ulinastatin group（n =10）.Aside from the normal group,all rats were exposed to smoke plus lipopolysaccharide tracheal instillation to establish the COPD model.Changes in symptoms,signs,and lung histology were observed.Lung function was measured with a spirometer.Serum cytokines were de-tected using enzyme-linked immunosorbent assay,and changes in the JAK/STAT pathway,MMP-9,and＆amp;nbsp;MMPs inhibitor 1 （TIMP1）were detected by immunohistochemistry,RT-PCR,and western blotting,re-spectively.Results：Compared with the normal group,lung tissue was damaged,and lung function was reduced in the model control group.Additionally,the levels of interleukin （IL）-1β,γinterferon （IFN-γ）,and IL-6 were higher,while IL-4 and IL-10 were lower in the model control group than those in the normal group.The expressions of JAK1,STAT3,p-STAT3,and MMP-9 mRNA and protein in lung tis-sue were higher,and TIMP1 mRNA and protein was lower in the model group compared with the normal group.After treatment,compared with the model group,the expression of inflammatory cytokines was lower in each treatment group,and expressions of JAK/STAT pathway,MMPs were lower.Conclusion：ulinastatin can improve the symptoms of COPD possibly by regulating the expression of the JAK1 /STAT3 pathway and MMP9 /TIMP1.
出处
《暨南大学学报（自然科学与医学版）》
CAS
CSCD
北大核心
2015年第6期496-502,共7页
Journal of Jinan University(Natural Science & Medicine Edition)
基金
国家自然科学基金项目(30971105)
关键词
乌司他丁
慢性阻塞性肺疾病
肺损伤
信号通路
Ulinastatin
chronic obstructive pulmonary disease
lung injury
signal pathway
