|
|
|
| Molecular mechanism of Qufeng Jiejing Prescription in regulating γδT cells to inhibit airway hyperresponsiveness in asthmatic mice |
| FAN Changzheng1 MAO Qing1 HONG Qiaoyu2 CUI Yun1 HE Yi1 ZHANG Qiong1 ZHANG Wenjiang1 |
1.Department of Pneumology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China;
2.Department of Traditional Chinese Medicine Rehabilitation, Beijing Health Vocational College, Beijing 101101, China |
|
|
|
Abstract Objective To investigate the molecular mechanism of Qufeng Jiejing Prescription in regulating γδT cells to inhibit airway hyperresponsiveness in asthmatic mice. Methods The Balb/c mouse model of asthma was established with the method of ovalbumin nasal drip, and the intervention was conducted with the drugs of Qufeng Jiejing Prescription. The intervention effect of Qufeng Jiejing Prescription on the molecular phosphorylation level of signaling pathway during activation of γδT cells was compared. Thirty experimental mice method was divided into 6 groups according to random number table, each group of 5 mice, respectively for the blank control group, asthma model group, Prednisone Acetate group (0.27 mg/d), Qufeng Jiejing Prescription low dose group (0.59 g/d), Qufeng Jiejing Prescription medium dose group (1.18 g/d), Qufeng Jiejing Prescription high dose group (2.36 g/d). Each group was treated 1 time/d and intervention for 7 days. After administration, the mice were anesthetized and sacrificed, and the γδT cells in the lung airway tissues were isolated, purified and amplified. The proliferation activity of the γδT cells was detected by CCK-8, and the phosphorylation levels of molecules in different signaling pathways were detected by Western blot. Results Compared with the blank control group, the activity of γδT cells in the asthma model group was significantly increased, with statistically significant difference (P ＜ 0.05). Compared with the asthma model group, there was no significant difference in the activity of γδT cells in the Qufeng Jiejing Prescription low dose group (P ＞ 0.05), while the activity of γδT cells in the medium, high dose groups of Qufeng Jiejing Prescription and the Prednisone Acetate group were significantly decreased (P ＜ 0.05). Compared with the blank control group, the protein expression levels of p-ERK1/2, p-P38 and β-catenin in the asthma model group increased, with statistically significant difference (P ＜ 0.05), while the protein expression levels of ERK1/2 and P38 showed no statistically significant difference (P ＞ 0.05). Compared with the asthma model group, the protein expression levels of p-ERK1/2, p-P38 and β-catenin in the low, medium and high dose groups of Qufeng Jiejing Prescription and the Prednisone Acetate group were decreased, with statistically significant differences (P ＜ 0.05). However, ERK1/2 protein expression level increased in the middle and high dose groups of Qufeng Jiejing Prescription and Prednisone Acetate group, and P38 protein expression level increased in the Qufeng Jiejing Prescription low dose group and Prednisone Acetate group, the differences were statistically significant (all P ＜ 0.05). Conclusion The possible molecular signaling pathway mechanism of the regulation of T cells to inhibit airway hyperresponsiveness in asthmatic mice is to inhibit the protein expression levels of p-ERK1/2, p-P38 and β-catenin, so as to reduce airway hyperresponsiveness in asthmatic mice and achieve the treatment of asthma.
|
|
|
|
|
|
[1] 中华医学会呼吸病学会哮喘学组.支气管哮喘防治指南（2016年版）[J].中华结核和呼吸杂志，2016，39（9）：675-697.
[2] 张雷英，吴建奇，刘静，等.γδT细胞参与呼吸道合胞病毒感染对气道变态炎症反应的影响作用[J].中华微生物学和免疫学杂志，2012，32（3）：234-238.
[3] Lu H，Li DJ，Jin LP. γδT cells and related diseases [J]. Am J Reprod Immunol，2016，75（6）：609-618. doi：10. 1111/aji.12495.
[4] Bonneville M，O′Brien RL，Born WK. Gammadelta T cell effector functions：a blend of innate programming and acpuired plasticity [J]. Nat Rev Irnrnunol，2010，10（7）：467-468.
[5] Brannan JD. Bronchial hyperresponsiveness in the assessment of asthma control：Airway hyperresponsiveness in asthma：its measurement and clinical significance [J]. Chest，2010，138（2 Suppl）：11S-17S.
[6] 曾胜，刘静，张雷英，等.γδT细胞在过敏性哮喘中作用研究的新进展[J].中国免疫学杂志，2013，29（4）：421-425.
[7] 樊长征，苗青，张燕萍.许建中从“虚、痰、毒、瘀”论治支气管哮喘的经验[J].光明中医，2011，26（4）：657-658.
[8] 樊长征，裴玉蓁，丛晓东，等.祛风解痉方药对支气管哮喘患者气道高反应性的影响[J].中医杂志，2018，59（24）：2107-2110.
[9] Kabelitz D，Marischen L，Oberg HH，et al. Epithelial defence by gamma delta T cells [J]. Int Arch Allergy Immunol，2015，137（1）：73-81.
[10] 樊长征，苗青.支气管哮喘气道高反应易感基因原钙黏蛋白1研究进展[J].中华哮喘杂志：电子版，2012，6（2）：135-136.
[11] 樊长征，裴玉蓁，张文江，等.风邪恋肺在支气管哮喘慢性持续期中的认识和临床运用[J].中国医药导报，2016， 13（1）：102-105.
[12] 王薇.种植体微纳米形貌对成骨细胞行为影响的分子机制研究[D].西安：第四军医大学，2013.
[13] Liang L，Li F，Bao A，et al. Activation of p38 mitogen-activated protein kinase in ovalbumin and ozone-induced mouse model of asthma [J]. Respirology，2013，18 Suppl 3：20-29.
[14] 潘伟东，王东军.ERK1/2研究进展及其与神经胶质瘤相关性[J].海南医学，2011，22（22）：121-124.
[15] 穆凯代斯·赛迪，杨晓红.p38 MAPK信号通路与糖皮质激素抵抗型哮喘的关系[J].医学综述，2019，25（4）：654-658.
[16] Onions ST，Ito K，Charron CE，et al. The discovery of narrow spectrum kinase inhibitors：New therapeutic agents for the treatment of COPD and steroid resistant asthma [J]. J Med Chem，2016，59（5）：1727-1746.
[17] Irusen E，Matthews JG，Takahashi A，et al. p38 Mitogen-activated protein kinase-induced glucocorticoid receptor phosphorylation reduces its activity：Role in steroid-insensitive asthma [J]. J Allergy Clin Immunol，2002，109（4）：649-657.
[18] 程云娟，罗新华，程明亮.人原发性肝癌组织中AEG-1、β-catenin和C-myc的表达及其意义[J].贵州医药，2015，39（11）：967-969.
[19] 莫文斌，唐玲荣，刘妍雨.Wnt信号通路分子调控细胞迁移的研究进展[J].中国中医药咨讯，2010，2（12）：200-201.
[20] 赵东康，骆伟伟，余水平，等.Wnt信号通路与肝纤维化发生发展的关系[J].临床肝胆病杂志，2018，34（11）：2415-2419.
[21] Luis TC，Naber BA，Roozen PP，et al. Canonical wnt signaling regulates hematopoiesis in a dosage-dependent fashion [J]. Cell Stem Cell，2011，9（4）：345-356. |
|
|
|
