血红素加氧酶-1对哮喘模型中Th1/Th2/Th17/Treg亚群及相关细胞因子分泌格局的影响  

Effect of heme oxygenase⁃1 on Th1/Th2/Th17/Treg subsets and secretion pattern of related cytokines in asthmatic model

作　　者：蔚京京[1] WEI Jingjing(Department of Pediatrics,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学儿科医学系,太原030001

出　　处：《山西医科大学学报》2024年第9期1177-1183,共7页Journal of Shanxi Medical University

基　　金：山西省自然科学研究面上项目(202203021211242)。

摘　　要：目的 探讨血红素加氧酶-1对哮喘动物模型中Th1/Th2/Th17/Treg亚群及相关细胞因子分泌格局的影响。方法将Balb/C小鼠随机分为5组:正常对照组、卵清蛋白(OVA)组、氯化血红素(Hemin)组、锡原卟啉(SnPP)组、Hemin+SnPP组,每组10只。OVA组使用OVA对小鼠进行致敏和激发建立哮喘模型,其他3个干预组在OVA致敏和激发前2d及第27天分别给予Hemin、SnPP或同时给予Hemin和SnPP溶液腹腔注射。造模成功后通过肺组织病理切片及支气管肺泡灌洗液(BALF)炎症细胞分类计数观察哮喘动物模型气道炎症程度,流式细胞计数法检测脾脏CD4+CD25+FoxP3+Treg细胞、CD4+IL-10R+IFN-γR+Treg1细胞和CD4+IL-17+Th17细胞的比例,ELISA方法检测血清及BALF中Th1/Th2/Th17/Treg相关细胞因子IL-4、IFN-γ、IL-2、IL-17、TNF-α、IL-10和TGF-β的水平,免疫组化测定肺组织IL-17的表达。结果(1)与正常对照组比较,其他四组小鼠肺组织均有不同程度的炎症细胞浸润,其中OVA组小鼠最严重,Hemin组最轻。与正常对照组比较,OVA组小鼠BALF中细胞总数和嗜酸性粒细胞(EOS)明显增多,脾脏组织中CD4+CD25+FoxP3+Treg细胞比例下降,CD4+IL-17+Th17细胞比例升高,血清中IL-4、TNF-α增多而IFN-γ、IL-2、IL-10和TGF-β减少,BALF中IL-17增多,肺组织IL-17阳性表达增多(均P<0.01);Hemin组BALF中细胞总数和EOS增多,CD4+CD25+FoxP3+Treg、CD4+IL-10R+IFN-γR+Treg1和CD4+IL-17+Th17细胞比例升高(均P<0.01),其余指标无明显变化;SnPP组和Hemin+SnPP组TNF-α以及Hemin+SnPP组CD4+CD25+FoxP3+Treg比例和IL-10水平差异无统计学意义,其余各指标变化趋势同OVA组(均P<0.01)。(2)与OVA组比较,Hemin组BALF中细胞总数和EOS明显减少,脾脏CD4+CD25+FoxP3+Treg细胞和CD4+IL-10R+IFN-γR+Treg1细胞比例均升高,CD4+IL-17+Th17细胞比例下降,除TGF-β外其他细胞因子变化差异均有统计学意义(均P<0.05)。其他两组变化趋势与OVA组基本相同,与Hemin组比较免疫失衡和炎症因子变�Objective To explore the effect of heme oxygenase-1(HO-1)on Th1/Th2/Th17/Treg subsets and the secretion pattern of related cytokines in asthmatic mouse model.Methods Balb/C mice were randomly divided into five groups:normal control group,ovalbumin(OVA)group,heme chloride(Hemin)group,tin protoporphyrin(SnPP)group,and Hemin+SnPP group,with 10 mice in each group.The mice in OVA group were sensitized and challenged to establish an asthma model,and the mice in the other three groups were intraperitoneally injected with Hemin,SnPP,Hemin+SnPP solution at day 2 before OVA sensitization and challenge and at day 27 respectively.Airway inflammation degree was detected by bronchoalveolar lavage fluid(BALF)cell counting and lung histo-pathology.The proportions of CD4+CD25+FoxP3+Treg,CD4+IL-10R+IFN-γR+Treg1 and CD4+IL-17+Th17 in splenic cells were mea-sured by flow cytometry,the levels of IL-4,IFN-γ,IL-2,IL-17,TNF-α,IL-10 and TGF-βin serum and BALF were analyzed by ELISA,and the expression of IL-17 in lung tissue was detected by immunohistochemistry.Results①Compared with normal control group,there were different degrees of inflammatory cell infiltration in the lung tissues in the other four groups,and it was the most severe in OVA group,and the lightest in Hemin group.Compared with normal control group,the numbers of total cells and eosinophils(EOS)in BALF were significantly increased in OVA group,the proportion of CD4+CD25+FoxP3+Treg cells in spleen tissue was de-creased,the proportion of CD4+IL-17+Th17 cells was increased,serum levels of IL-4 and TNF-αwere increased,and serum levels of IFN-γ,IL-2,IL-10 and TGF-βwere decreased,IL-17 level in BALF was increased,and the positive expression of IL-17 in lung tissue was increased(all P<0.01).Compared with normal control group,the numbers of total cells and EOS in BALF,and the propor-tions of CD4+CD25+FoxP3+Treg,CD4+IL-10R+IFN-γR+Treg1 and CD4+IL-17+Th17 cells were increased in Hemin group(all P<0.01),and the other indexes showed no significant change.Compared with normal

关 键 词：哮喘 血红素加氧酶-1 T细胞亚群 免疫调节 炎症 细胞因子 

分 类 号：R562.25[医药卫生—呼吸系统]