差异表达的microRNA可能通过抑制MRGPRX2治疗过敏性哮喘  

Differential expression of microRNAs treats allergic asthma probably by suppressing MRGPRX2

作　　者：吴媛媛[1] 王珏 刘昀[1] 刘艳琴[1] 孙秀珍[1] WU Yuanyuan;WANG Jue;LIU Yun;LIU Yanqin;SUN Xiuzhen(Department of Respiratory and Critical Care Medicine,Se-cond Affiliated Hospital,Xi’ an Jiaotong University,Xi’ an 710004,China;School of Pharmacy,Xi’ an Jiaotong University)

机构地区：[1]西安交通大学第二附属医院呼吸与危重症医学科,西安710004 [2]西安交通大学药学院

出　　处：《山西医科大学学报》2019年第5期561-565,共5页Journal of Shanxi Medical University

摘　　要：目的探讨microRNA和MRGPRX2的相互关系及其对过敏性哮喘的作用。方法 C57BL/6小鼠分为以下四组:正常对照组(control)、过敏性哮喘组(AR组)、MRGPRB2-/-对照组(敲除MRGPRX2基因)、MRGPRB2-/-AR组(敲除MRGPRX2基因,给予OVA刺激)。应用卵清蛋白(OVA)诱导小鼠哮喘模型。通过Target Scan/microRNA. org/等在线数据库预测共同靶向h MRGPRX2及小鼠MRGPRB2的microRNA分子; real-time PCR检测各组小鼠肺组织中miR-212(-3p)、miR-132(-3p)、miR-590-3p、miR-495(-3p)的表达水平; HE染色观察气道炎症; Western blot检测MRGPRB2表达水平。结果与正常对照组比较,哮喘组小鼠肺组织中miR-212(-3p)、miR-132(-3p)、miR-590-3p、miR-495(-3p)均存在一定程度的下降,差异具有统计学意义(P <0. 05); MRGPRB2-/-AR组小鼠(敲除MRGPRX2基因,给予OVA刺激),与哮喘组相比较,其肺组织中miR-212(-3p)、miR-132(-3p)、miR-590-3p、miR-495(-3p)的相对表达水平回升,差异均有统计学意义(P <0. 05)。哮喘组小鼠与正常对照组小鼠和MRGPRB2-/-AR小鼠相比,气管周围可见明显炎性细胞浸润,上皮损伤、脱落,且肺组织中MRGPRB2表达水平较高(P <0. 05)。结论 miR-212(-3p)、miR-132(-3p)、miR-590-3p、miR-495(-3p)在OVA诱导的过敏性哮喘小鼠模型中存在差异表达,差异表达的microRNA可能通过抑制靶基因MRGPRX2的表达进而抑制哮喘气道炎症。Objective To explore the effect of microRNAs and MRGPRX2 on allergic asthma( AR) in a murine model. Methods C57 BL/6 mice were divided into four groups: control group,AR group,MRGPRB2-/-group( MRGPRX2 gene deletion) and MRGPRB2-/-AR group. The ovalbumin( OVA) was applied to induce the asthma model. MRGPRB2-/-mice were sensitized with OVA in MRGPRB2-/-AR group. Online database such as Target Scan/microRNA. org/was used to predict microRNAs molecules targeting MRGPRB2 or h MRGPRX2. The levels of miR-212(-3 p),miR-132(-3 p),miR-590-3 p,miR-495(-3 p) in the lung tissues were measured by real-time PCR. Lung sections were stained with haematoxylin and eosin staining( HE) to assess inflammatory cell infiltration,and Western blot was used to measure the protein expression of MRGPRB2. Results The levels of miR-212(-3 p),miR-132(-3 p),miR-590-3 p,miR-495(-3 p) were significantly lower in AR group than in control group( P < 0. 05 or P < 0. 01),while the expression levels of miR-212(-3 p),miR-132(-3 p),miR-590-3 p,miR-495(-3 p) in MRGPRB2-/-AR group were significantly higher than those in AR group( P < 0. 05). The OVA-induced mice developed severe airway inflammatory responses,including infiltrating around respiratory tract and vessels,but there was no obvious inflammatory cell infiltration in lung tissues in control group and MRGPRB2-/-group. MRGPRB2 expression in lung tissue was significantly higher in AR group than in control group and MRGPRB2-/-group( P < 0. 05). Conclusion These related microRNAs have differential expression in murine asthma model induced by OVA,and the microRNA could inhibit airway inflammation of allergic asthma by suppressing MRGPRX2 expression.

关 键 词：过敏性哮喘 mas基因相关G蛋白耦联受体 MICRORNA 

分 类 号：R562.25[医药卫生—呼吸系统]