摘要
目的:观察MKK34多肽(TSLP碳端α螺旋区域)对屋尘螨(HDM)哮喘小鼠气道炎症及气道上皮细胞连接蛋白β-catenin的影响。方法:将32只BALB/c小鼠随机分为4组。哮喘组每周连续5 d滴鼻给予HDM,预处理组在给予HDM前1 h滴鼻给予MKK34多肽,8周后,动物肺功能测定和病理染色来评估哮喘的情况,检测各组小鼠的肺泡灌洗液IL-4、IFN-γ及血清Ig E,用免疫组化及Western blot测定肺组织β-catenin的分布和表达及p-ERK1/2、t-ERK1/2的表达。结果:HDM哮喘组气道反应性、肺泡灌洗液IL-4和血清Ig E均较对照组增高,MKK34预处理组较哮喘组上述指标都有所改善。肺组织HE染色示哮喘组具有气道炎症的典型病变,而MKK34预处理组炎症明显轻于哮喘组,免疫组化及Western blot结果示,对照组在气道上皮细胞的细胞膜连接处紧密的分布着β-catenin蛋白,而哮喘组β-catenin分布混乱、减少,MKK34预处理组能减少β-catenin的破坏,在哮喘组p-ERK1/2表达明显增加,MKK34多肽预处理组较哮喘组减少。结论:MKK34多肽可能通过抑制ERK的磷酸化来改善HDM哮喘小鼠的气道炎症及气道上皮细胞连接蛋白β-catenin的破坏。
Objective To explore the role of MKK34 （ a peptide spanning a C-terminal α-helical region in TSLP ） on airway inflammation and β-catenin of airway epithelium in a HDM-induced mouse asthma. Methods 32 male BALB/c mice were randomly divided into control, MKK34, asthma and MKK34 ＋ HDM groups. The mice in the asthma group were exposed to HDM for five consecutive days and the MKK34 ＋ HDM group was pretreated with MKK34 1 h prior to the HDM intranasally treated. After 8 weeks＇ treatment, animal lung function test and pathological staining were performed to evaluate the asthma situation, IL-4, IFN-γ in bronchoalveolar lavage fluid and IgE in the serum were detected, immunohistochemistry and western blot were used to assess β-catenin and p-ERK, t-ERK levels. Results Airway reactivity, IL-4 and IgE in the asthma group were significantly higher than that in the control group. Treatment with MKK34 significantly decreased airway hyperresponsiveness, IL-4 and IgE. HE staining demonstrated the chronic bronchitic inflammation in the lungs of asthma group. β-catenin in the control group was distributed evenly at the cytomembrane of epithelial cells. In the asthma group, β- catenin was disordered in epithelial cells and its expression was decreased. Treatment with MKK34 ameliorated the damage of β-catenin and chronic bronchitic inflammation. The protein levels of p-ERK1/2 increased obviously in the asthma group. The pretreated group significantly decreased the expression of p-ERK1/2. Conclusions MKK34 can ameliorate the airway inflammation and the destruction of β-catenin of airway epithelium in a HDM-induced mouse asthma. The ERK pathway may play a role in this process.
作者
胡亚惠
董航明
刘来昱
黄超文
罗丽珊
万轩
赵海金
蔡绍曦
HU Yahui DONG Hangming LIU Laiyu HUANG Chaowen LUO Lishan WAN Xuan ZHAO Haijin CAI Shaoxi(Department of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China)
出处
《实用医学杂志》
CAS
北大核心
2017年第4期543-547,共5页
The Journal of Practical Medicine
基金
国家自然科学基金(编号:81270087,81470228,81670026)
国家重点研发计划(编号:2016YFC0905803)
