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多肽SJMHE1通过调节miR-21和miR-17的表达对哮喘小鼠发挥治疗作用

Polypeptide SJMHE1 plays a therapeutic role in asthmatic mice by regulating miR-21 and miR-17 expression
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摘要 目的探究血吸虫来源的多肽SJMHE1对哮喘小鼠的治疗效果及微小RNA-21(miR-21)和微小RNA-17(miR-17)在这一过程中的作用。方法将所有小鼠随机分为对照组、哮喘组、哮喘/PBS组、哮喘/SJMHE1组。除对照组外,其余3组小鼠均使用卵清蛋白(OVA)诱导哮喘模型。小鼠肺部组织HE染色评估气道炎症。小鼠支气管肺泡灌洗液(BALF)分类和计数,ELISA测定血清特异性IgE表达。流式细胞术分析Th1、Th2、Th17、Treg细胞亚群的分布。实时荧光定量PCR(qRTPCR)检测小鼠肺中Th相关转录因子和细胞因子的表达及miR-21和miR-17的水平,Western blot检测p-STAT3和PTEN蛋白的表达。结果与对照组相比,哮喘组小鼠气道炎症增加,BALF中炎性细胞数增加(P<0.001),血清IgE表达水平升高(P<0.001),Th1、Treg细胞的比例、相关转录子和细胞因子的表达下降,Th2、Th17细胞比例及相关转录子和细胞因子的表达升高(P<0.05),miR-21和miR-17表达升高(P<0.001),p-STAT3表达升高,PTEN表达降低;与哮喘/PBS组相比,哮喘/SJMHE1组小鼠上述指标的表达发生逆转。结论多肽SJMHE1可能通过miR-21、miR-17调节哮喘小鼠Th1/Th2/Th17/Treg细胞平衡发挥治疗作用。 This study was designed to explore the therapeutic effect of the Schistosoma japonicum-derived peptide SJMHE1 in asthmatic mice and the roles of microRNA-21(miR-21)and miR-17 in this process.Mice were randomly divided into control group,asthma group,asthma+PBS group,and asthma+SJMHE1 group.Asthma model was induced with the ovalbumin(OVA)in mice.Airway inflammation was assessed by histopathologic sections of mouse lungs;bronchoalveolar lavage fluid(BALF)was sorted and counted,and the expression level of OVA-specific IgE in mouse serum was measured by ELISA;the distribution of T helper(Th)cells was analyzed by flow cytometry.qRT-PCR was used to detect the expression of Th-associated transcription factors and cytokines,the levels of miR-21 and miR-17 in the lungs of mice;Western blot was used to detected the protein expression of phosphorylated signal transducer and activator of transcription 3(p-STAT3)and phosphatase and tensin homolog(PTEN).Compared with the control group,mice in the asthma group demonstrated increases in airway inflammation,eosinophil and neutrophil counts in the BALF,serum IgE expression levels(P<0.001),proportions of Th2 and Th17 cells,expressions of related transcripts and cytokines(P<0.05),expression of miR-21 and miR-17(P<0.001),and expression of p-STAT3,while decreases in proportions of Th1 and Treg cells,expression of related transcripts and cytokines,and expression of PTEN.All indicators mentioned above was reversed in mice of the asthma/SJMHE1 group,as compared with the asthma/PBS group.In conclusion,the peptide SJMHE1 regulates Th1/Th2/Th17/Treg cell balance via miR-21 and miR-17,thus plays a therapeutic role in asthmatic mice.
作者 郑玉 丁超 陈龙 徐国新 ZHENG Yu;DING Chao;CHEN Long;XU Guoxin(Department of Clinical Laboratory,Affiliated Zhangjiagang Hospital of Soochow University,Zhangjiagang 215600,China)
出处 《免疫学杂志》 CAS CSCD 2024年第6期489-495,共7页 Immunological Journal
基金 苏州市2022年度第十六批科技发展计划项目(SLT2022001) 张家港市科技计划项目(ZKS2041) 张家港市卫健委青年科技项目(ZJGQNKJ202126)。
关键词 SJMHE1 哮喘 微小RNA T辅助细胞 P-STAT3 PTEN SJMHE1 Asthma microRNA T helper cells p-STAT3 PTEN
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