miR-200介导的IL-33表达参与支气管哮喘发展过程的临床和小鼠实验研究  

Expression of IL-33 mediated by miR-200 is involved in the development process of clinical and mouse experimental studies of bronchial asthma

作　　者：刘婷婷[1] 李晓利[2] 李莉红[1] 王亚康 王军宁 LIU Ting-ting;LI Xiao-li;LI Li-hong(Department of Cadre,Xi'an First Hospital,Xi'an Shaanxi 710002,China;Department of Respiratory and Gastroenterology,Honghui Hospital,Xi'an Jiaotong University,Xi'an Shaanxi 710054,China)

机构地区：[1]西安市第一医院干三科,陕西西安710002 [2]西安交通大学附属红会医院呼吸消化科,陕西西安710054 [3]西安交通大学附属红会医院关节外科,陕西西安710054

出　　处：《临床和实验医学杂志》2019年第22期2409-2413,共5页Journal of Clinical and Experimental Medicine

基　　金：陕西省自然科学基础研究计划项目(编号:2019JQ-536)

摘　　要：目的探讨miR-200对支气管哮喘发病过程的影响及潜在机制。方法选取22例为哮喘患者为哮喘组,14例正常人为正常组,检测两组支气管肺泡灌洗液(BALF)中miR-200a、miR-200b、miR-200c和血清中IL-33表达,分析IL-33与miR-200a、miR-200b、miR-200c的相关性。选取40只健康雄性BALB/c小鼠随机分为4组:对照组、卵清蛋白(OVA)组、OVA+miR-200b组、OVA+miR-200c组,每组各10只。采用OVA建立实验性哮喘小鼠模型,之后用miR-200b或miR-200c寡核苷酸通过鼻腔给药干预OVA小鼠,对照组小鼠用生理盐水代替。检测各组小鼠对不同浓度醋甲胆碱的气道阻力,及血清、BALF及肺组织中IL-33的含量,肺组织中miR-200b、miR-200c、IL-4、IL-5、IL-13的水平。结果与正常组比较,哮喘组患者BALF中miR-200b和miR-200c的表达显著降低(P<0.05),miR-200a的表达无显著变化(P>0.05),此外哮喘组患者血清IL-33的含量显著增加(P<0.05)。哮喘组患者血清IL-33的含量与BALF中miR-200b和miR-200c的表达呈显著负相关(P<0.05)。与对照组比较,OVA组小鼠肺组织中miR-200b和miR-200c的表达显著降低(P<0.05),血清、BALF及肺组织中IL-33的含量显著增加(P<0.05),肺组织中炎症因子IL-4、IL-5和IL-13含量显著增加(P<0.05),对8 mg/ml、12 mg/ml和16 mg/ml的醋甲胆碱的气道阻力显著增加(P<0.05)。与OVA组比较,OVA+miR-200b组和OVA+miR-200c组小鼠上述指标均逆转(P<0.05)。结论miR-200b/c表达降低与支气管哮喘的发展有密切关系,其可通过调节IL-33信号通路,可作为哮喘治疗的靶点之一。Objective To explore the effect and potential mechanism of miR-200 on the pathogenesis of bronchial asthma.Methods 22 patients with asthma were selected as asthma group,and 14 normal subjects were normal group.The expression of miR-200a,miR-200b,miR-200c in bronchoalveolar lavage fluid(BALF)and IL-33 in serum was detected.Correlation of IL-33 with miR-200a,miR-200b,miR-200c was analyzed.40 healthy male BALB/c mice were randomly divided into 4 groups,including control group,ovalbumin(OVA)group,OVA+miR-200b group,OVA+miR-200c group,with 10 mice in each group.OVA was used to establish a mouse model of experimental asthma,and then OVA mice were treated with nasal administration of miR-200b or miR-200c oligonucleotides.The control group mice were replaced with saline.The airway resistance to different concentrations of methacholine,the levels of IL-33 in serum,BALF and lung tissues,and the levels of miR-200b,miR-200c,IL-4,IL-5,IL-13 in lung tissue were measured in each group.Results Compared with the normal group,the expression of miR-200b and miR-200c in BALF was significantly lower than that in the asthma group(P<0.05),and the expression of miR-200a had not significantly changed(P>0.05).In addition,the content of serum IL-33 was significantly increased in the asthma group compared to normal group(P<0.05).The level of serum IL-33 in the asthma group were significantly negatively correlated with the expression of miR-200b and miR-200c in BALF(P<0.05).Compared with the control group,the expressions of miR-200b and miR-200c in the lung tissue in OVA group were significantly decreased(P<0.05),the content of IL-33 in serum,BALF and lung tissue were significantly increased(P<0.05),the levels of inflammatory factors IL-4,IL-5 and IL-13 in the lung tissues were significantly increased(P<0.05),and the airway resistance to methamphetamine at dosage of 8 mg/ml,12 mg/ml and 16 mg/ml were significantly increased in OVA group(P<0.05).Compared with the OVA group,the above-mentioned indicators were reversed in the OVA+miR-200b group

关 键 词：支气管哮喘 临床研究 小鼠实验 miR-200 IL-33 

分 类 号：R562.25[医药卫生—呼吸系统]