[1]张晶 吴晓晨 张家旺 谢雨婕 钟华胜.全真一气汤对肾气虚型哮喘大鼠转录因子FOXP3/RORγt及Th17/Treg免疫失衡的影响[J].现代中医药,2023,(06):096-102.[doi:10.13424/j.cnki.mtcm.2023.06.020]
点击复制

全真一气汤对肾气虚型哮喘大鼠转录因子FOXP3/RORγt及Th17/Treg免疫失衡的影响()
分享到:

《现代中医药》[ISSN:1006-6977/CN:61-1281/TN]

卷:
期数:
2023年06期
页码:
096-102
栏目:
出版日期:
2023-12-08

文章信息/Info

文章编号:
1672-0571(2023)06-0096-07
作者:
张晶1 吴晓晨1 张家旺1 谢雨婕1 钟华胜2
1.福建中医药大学附属第二人民医院,福建 福州 350003;
2.龙岩市上杭县医院,福建 上杭 364200
关键词:
关键词:全真一气汤支气管哮喘辅助型T细胞17/调节性T细胞维甲酸相关孤独核受体-γt叉头状转录因子细胞因子
分类号:
R256.12
DOI:
10.13424/j.cnki.mtcm.2023.06.020
文献标志码:
A
摘要:
摘 要:目的 观察全真一气汤对肾气虚型哮喘大鼠Th17/Treg及相关细胞因子(IL-6、IL-17、IL-10、IL-35)和转录因子维甲酸相关孤独核受体-γt(OrPhan nuclear recePtor gamma t,RORγt)、叉头状转录因子(forkhead transcriPtion factor P3,FOXP3)的影响,探讨全真一气汤调控哮喘气道炎症的机制。方法 将24只SD雄性大鼠随机分为空白组、模型组、全真一气汤低剂量治疗组(8.33g·kg-1)和全真一气汤高剂量治疗组(33.32 g·kg-1),每组6只。模型组与低、高剂量治疗组予卵蛋白1mg、氢氧化铝凝胶10 mg的混悬液1 mL致敏,1%的卵清蛋白超声雾化吸入以激发哮喘,进行惊恐刺激,负重游泳直至力竭等进行肾气虚型哮喘大鼠造模,造模成功后开始药物干预。空白组和模型组予生理盐水3 mL灌服,治疗组按低、高剂量予全真一气汤3 mL灌服,每日1次,连服30 d。实时荧光定量聚合酶链式反应(Real time Quanti tative PCR,qRT-PCR)检测各组大鼠肺组织中FOXP3、RORγt mRNA水平,流式细胞术检测外周血Th17、Treg细胞百分比,酶联免疫吸附实验(Enzyme Linked Immunosorbent Assay,ELISA)检测血清IL-6、IL-17、IL-10、IL-35细胞因子含量。结果 与空白组相比,模型组血Th17细胞比例、血清IL-6、IL-17含量及相关肺组织中RORγt mRNA和蛋白表达水平显著升高(P<0.05),模型组Treg细胞比例、血清IL-10、IL-35含量及相关肺组织中FOXP3 mRNA和蛋白表达水平明显降低(P<0.05);与模型组相比,全真一气汤低、高剂量组血Th17细胞百分比、血清IL-6、IL-17含量及肺组织RORγt mRNA和蛋白的表达明显减少(P<0.05),高剂量组血Treg细胞百分比显著升高(P<0.05),但全真一气汤低剂量组血Treg细胞百分比无显著变化(P>0.05),高剂量组血清IL-10含量增加(P<0.05),全真一气汤低剂量组IL-10含量亦增加,但差异无统计学意义(P>0.05),两组血清IL-35含量、FOXP3 mRNA及蛋白的表达同时明显升高(P<0.05);与全真一气汤低剂量组相比,高剂量组Th17细胞百分比明显降低(P>0.05),IL-17亦降低(P>0.05),IL-6含量及RORγt表达减少(P<0.05),高剂量组IL-35含量及Treg相关的FOXP3表达增加(P<0.05)。结论 全真一气汤低剂量组、全真一气汤高剂量组全真一气汤均可降低Th17细胞及相关促炎因子IL-6、IL-17的含量,抑制RORγt的表达;高剂量组可以升高Treg细胞百分比,而全真一气汤低剂量组对Treg细胞百分比影响则不明显,但都可以上调FOXP3的表达,促进相关抑炎因子IL-10、IL-35分泌。摘 要:目的 观察全真一气汤对肾气虚型哮喘大鼠Th17/Treg及相关细胞因子(IL-6、IL-17、IL-10、IL-35)和转录因子维甲酸相关孤独核受体-γt(OrPhan nuclear recePtor gamma t,RORγt)、叉头状转录因子(forkhead transcriPtion factor P3,FOXP3)的影响,探讨全真一气汤调控哮喘气道炎症的机制。方法 将24只SD雄性大鼠随机分为空白组、模型组、全真一气汤低剂量治疗组(8.33g·kg-1)和全真一气汤高剂量治疗组(33.32 g·kg-1),每组6只。模型组与低、高剂量治疗组予卵蛋白1mg、氢氧化铝凝胶10 mg的混悬液1 mL致敏,1%的卵清蛋白超声雾化吸入以激发哮喘,进行惊恐刺激,负重游泳直至力竭等进行肾气虚型哮喘大鼠造模,造模成功后开始药物干预。空白组和模型组予生理盐水3 mL灌服,治疗组按低、高剂量予全真一气汤3 mL灌服,每日1次,连服30 d。实时荧光定量聚合酶链式反应(Real time Quanti tative PCR,qRT-PCR)检测各组大鼠肺组织中FOXP3、RORγt mRNA水平,流式细胞术检测外周血Th17、Treg细胞百分比,酶联免疫吸附实验(Enzyme Linked Immunosorbent Assay,ELISA)检测血清IL-6、IL-17、IL-10、IL-35细胞因子含量。结果 与空白组相比,模型组血Th17细胞比例、血清IL-6、IL-17含量及相关肺组织中RORγt mRNA和蛋白表达水平显著升高(P<0.05),模型组Treg细胞比例、血清IL-10、IL-35含量及相关肺组织中FOXP3 mRNA和蛋白表达水平明显降低(P<0.05);与模型组相比,全真一气汤低、高剂量组血Th17细胞百分比、血清IL-6、IL-17含量及肺组织RORγt mRNA和蛋白的表达明显减少(P<0.05),高剂量组血Treg细胞百分比显著升高(P<0.05),但全真一气汤低剂量组血Treg细胞百分比无显著变化(P>0.05),高剂量组血清IL-10含量增加(P<0.05),全真一气汤低剂量组IL-10含量亦增加,但差异无统计学意义(P>0.05),两组血清IL-35含量、FOXP3 mRNA及蛋白的表达同时明显升高(P<0.05);与全真一气汤低剂量组相比,高剂量组Th17细胞百分比明显降低(P>0.05),IL-17亦降低(P>0.05),IL-6含量及RORγt表达减少(P<0.05),高剂量组IL-35含量及Treg相关的FOXP3表达增加(P<0.05)。结论 全真一气汤低剂量组、全真一气汤高剂量组全真一气汤均可降低Th17细胞及相关促炎因子IL-6、IL-17的含量,抑制RORγt的表达;高剂量组可以升高Treg细胞百分比,而全真一气汤低剂量组对Treg细胞百分比影响则不明显,但都可以上调FOXP3的表达,促进相关抑炎因子IL-10、IL-35分泌。

参考文献/References:

[1]Papi A,Brightling C,Pedersen SE,et al.Asthma[J].The Lancet,2018,391(10122):783-800.
[2]Zou XL,Chen ZG,Zhang TT,et al.Th17/Treg homeostasis,but not Th1/Th2 homeostasis,is implicated in exacerbation of human bronchial asthma[J].Therapeutics and Clinical Risk Management,2018,14:1627-1636.
[3]Zhou YM,Zhao HH,Wang TS,et al.Anti-inflammatory and anti-asthmatic effects of TMDCT decoction in eosinophilic asthma through treg/Th17 balance[J].Frontiers in Pharmacology,2022,13:819728.
[4]Li CC,Sheng AQ,Jia XX,et al.Th17/Treg dysregulation in allergic asthmatic children is associated with elevated Notch expression[J].The Journal of Asthma:Official Journal of the Association for the Care of Asthma,2018,55(1):1-7.
[5]Lamb D,De Sousa D,Quast K,et al.RORγt inhibitors block both IL-17 and IL-22 conferring a potential advantage over anti-IL-17 alone to treat severe asthma
[J].Respiratory Research,2021,22(1):158.
[6]Chen TT,Hou XX,Ni YM,et al.The imbalance of FOXP3/GATA3 in regulatory T cells from the peripheral blood of asthmatic patients[J].Journal of Immunology Research,2018,2018:3096183.
[7]张晶,陈志斌,王春娥,等.基于气道炎症调控的全真一气汤干预肾气虚型哮喘大鼠的机制研究[J].中国中医急症,2019,28(8):1354-1357.
[8]张晶,严桂珍.全真一气汤治疗肾气虚型支气管哮喘缓解期32例疗效观察[J].福建中医药,2016,47(3):40-42.
[9]孟鹏飞,吕岳.简述用卵蛋白制作大鼠哮喘模型的要点[J].甘肃中医学院学报,2011,28(2):27-29.
[10]郑小伟,宋红,王颖,等.肾气虚哮喘模型及中西药联合干预的实验研究[J].浙江中医杂志,2012,47(2):129-131.
[11]胡健,张至强,曾时杰,等.三拗汤治疗支气管哮喘的研究进展[J].陕西中医药大学学报,2017,40(6):130-133.
[12]周进进,王娟,李晓娜.哮喘儿童IL-17A rs2275913基因多态性的临床意义[J].中国妇幼健康研究,2021,32(10):1436-1440.
[13]Wang LL,Wan HY,Tang W,et al.Critical roles of adenosine A2A receptor in regulating the balance of Treg/Th17 cells in allergic asthma[J].The Clinical Respiratory Journal,2018,12(1):149-157.
[14]Ding FX,Fu Z,Liu B.Lipopolysaccharide exposure alleviates asthma in mice by regulating Th1/Th2 and treg/Th17 balance[J].Medical Science Monitor:International Medical Journal of Experimental and Clinical Research,2018,24:3220-3229.
[15]雷艳青,陈波.六味地黄丸联合西药对支气管哮喘患者免疫功能的影响[J].陕西中医,2017,38(4):461-462.
[16]Kudo M,Melton AC,Chen C,et al.IL-17A produced by αβ T cells drives airway hyper-responsiveness in mice and enhances mouse and human airway smooth muscle contraction[J].Nature Medicine,2012,18(4):547-554.
[17]Annunziato F,Cosmi L,Liotta F,et al.Defining the human T helper 17 cell phenotype[J].Trends in Immunology,2012,33(10):505-512.
[18]Bonser LR,Erle DJ.Airway mucus and asthma:the role of MUC5AC and MUC5B[J].Journal of Clinical Medicine,2017,6(12):112.
[19]Suzuki Y,Maazi H,Sankaranarayanan I,et al.Lack of autophagy induces steroid-resistant airway inflammation[J].Journal of Allergy and Clinical Immunology,2016,137(5):1382-1389.e9.
[20]Al Heialy S,Gaudet M,Ramakrishnan RK,et al.Contribution of IL-17 in steroid hyporesponsiveness in obese asthmatics through dysregulation of glucocorticoid receptors α and Β[J].Frontiers in Immunology,2020,11:1724.
[21]Yu Q,Shi YJ,Shu C,et al.Andrographolide inhibition of Th17-regulated cytokines and JAK1/STAT3 signaling in OVA-stimulated asthma in mice[J].Evidence-Based Complementary and Alternative Medicine:ECAM,2021,2021:6862073.
[22]Fasching P,Stradner M,Graninger W,et al.Therapeutic potential of targeting the Th17/treg axis in autoimmune disorders[J].Molecules,2017,22(1):134.
[23]Xin L,Gao JJ,Ge XH,et al.Increased pro-inflammatory cytokine-secreting regulatory T cells are correlated with the plasticity of T helper cell differentiation and reflect disease status in asthma[J].Respiratory Medicine,2018,143:129-138.
[24]Shaaban R,Zureik M,Soussan D,et al.Rhinitis and onset of asthma:a longitudinal population-based study[J].The Lancet,2008,372(9643):1049-1057.
[25]Ming MY,Luo ZX,Lv SQ,et al.Inactivated Mycobacterium phlei inhalation ameliorates allergic asthma through modulating the balance of CD4+CD25+ regulatory T and Th17 cells in mice[J].Iranian Journal of Basic Medical Sciences,2016,19(9):953-959.
[26]叶峥嵘,孟淑华.对中医药免疫研究的思考[J].陕西中医药大学学报,2017,40(5):10-12,18.
[27]吴芳,张宏方.中医平衡系统与西医免疫—监视—抑瘤平衡理论的探讨[J].现代中医药,2014,34(6):62-64.[知网]
[28]冯兆张.冯氏锦囊秘录[M].田思胜,校注.北京:中国中医药出版社,1996:526.
[29]李信翰,张建伟.中国古代医易学说探究[J].现代中医药,2018,38(1):58-62,65.

相似文献/References:

[1]杨继 王强 **张垚.祛风解痉法治疗支气管哮喘慢性持续期探究[J].现代中医药,2018,(06):095.[doi:10.13424/j.cnki.mtcm.2018.06.033]
 Yang Ji Wang Qiang.Treatment of Chronic Persistent Bronchial Asthma by Dispelling Pathogenic Wind for Resolving Convulsion[J].Modern Traditional Chinese Medicine,2018,(06):095.[doi:10.13424/j.cnki.mtcm.2018.06.033]

备注/Memo

备注/Memo:
基金项目:福建省自然基金面上项目(2020J01245)
更新日期/Last Update: 2023-11-23