晚期糖基化终末产物受体促进甲苯二异氰酸脂哮喘小鼠MUC5AC表达及气道黏液高分泌

发布时间：2018-03-08 12:53

本文选题：甲苯二异氰酸酯哮喘　切入点：晚期糖基化终末产物受体　出处：《南方医科大学学报》2017年10期 　论文类型：期刊论文

【摘要】：目的探讨晚期糖基化终末产物受体(RAGE)信号对甲苯二异氰酸脂(TDI)哮喘小鼠黏蛋白MUC5AC表达及气道黏液分泌的影响。方法在体内水平上建立TDI小鼠哮喘模型,实验分4组:对照组、TDI溶剂(AOO)致敏激发组、TDI致敏激发组、RAGE抑制剂处理组。采用糖原染色评估各组间气道黏液分泌情况,Western blotting及免疫组化法检测MUC5AC表达水平。同时通过Western blotting检测各组间细胞外调节蛋白激酶(ERK)通路磷酸化水平。在体外水平配制TDI-人血清白蛋白(TDIHSA)复合物,刺激人支气管上皮细胞(16HBE)及经慢病毒转染空载体和sh RNA-RAGE载体的人支气管上皮细胞,检测各组MUC5AC及ERK通路分子表达情况,加入ERK抑制剂U0126后,进一步评估MUC5AC mRNA表达情况。结果与对照组相比,TDI哮喘组小鼠糖原染色阳性率及MUC5AC表达升高(P0.05),p-ERK表达增多(P0.05),RAGE抑制剂处理组糖原染色阳性率及MUC5AC表达较TDI组减少(P0.05)。同时,p-ERK表达下降(P0.05)。体外水平,与对照组相比,TDI-HSA处理组MUC5AC mRNA及p-ERK表达增多(P0.05),sh RNA-RAGE组MUC5AC mRNA及p-ERK表达下调(P0.05),ERK抑制剂预处理组,MUC5AC mRNA表达下调(P0.05)。结论 TDI小鼠哮喘模型下RAGE可能通过激活ERK通路促进黏蛋白MUC5AC的表达及黏液高分泌的发生。
[Abstract]:Objective to investigate the effect of advanced glycation end product receptor (RAGE) signal of two toluene isocyanate (TDI) of asthmatic mice viscosity influence the protein expression of MUC5AC and airway mucus secretion. Methods TDI mice model of asthma is established in vivo, were divided into 4 groups: control group, TDI solvent (AOO) sensitized group TDI, sensitized group, RAGE inhibitor treatment group. The glycogen staining was assessed between airway mucus secretion, Western and blotting were detected by immunohistochemistry. The expression level of MUC5AC and Western by blotting to detect the extracellular regulated protein kinase (ERK) pathway of phosphorylation in vitro. The level of preparation of human serum albumin (TDI- TDIHSA) complexes, stimulation of human bronchial epithelial cells (16HBE) and empty vector transfected by lentivirus vector of RNA-RAGE and SH in human bronchial epithelial cells, the expression of MUC5AC was detected and the ERK pathway, adding ERK suppression Preparation of U0126, further evaluation of MUC5AC expression of mRNA. Results compared with the control group, asthma group TDI mice glycogen staining positive rate and increase the expression of MUC5AC (P0.05), the increased expression of p-ERK (P0.05), RAGE inhibitor treatment group glycogen staining positive rate and expression of MUC5AC was lower than TDI group (P0.05). At the same time, decreasing the expression of p-ERK (P0.05). In vitro, compared with the control group, TDI-HSA group and MUC5AC mRNA increased the expression of p-ERK (P0.05), RNA-RAGE group MUC5AC mRNA expression of SH and p-ERK (P0.05), preconditioning group ERK inhibitors, MUC5AC mRNA expression (P0.05). Conclusion the model of TDI mouse asthma RAGE may activate ERK pathway to promote the expression of mucin MUC5AC and mucus hypersecretion.

【作者单位】：南方医科大学南方医院呼吸与危重症医学科//慢性气道疾病实验室;
【基金】：国家自然科学基金(81670026) 国家重点研发计划精准医学研究发展计划(2016YFC0905800) 广东省自然科学基金(2015A030313236) 广东省科技计划项目(2016A020215117)~~
【分类号】：R562.25

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