瞬时感受器电位香草酸受体4型通道蛋白在气道压力诱导大鼠气道黏液高分泌中的作用  

Role of transient receptor potential vanilloid 4 in airway mucous hypersecretion induced by high airway pressure in rats

作　　者：吴砚樵[1] 周向东[1] 

机构地区：[1]重庆医科大学附属第二医院呼吸内科,重庆400010

出　　处：《第三军医大学学报》2011年第13期1385-1387,共3页Journal of Third Military Medical University

摘　　要：目的探讨机械通气产生的气道压力对大鼠气道黏液高分泌的影响及机制。方法 48只SD大鼠分为4组,实施麻醉和气管切开后接小动物呼吸机进行机械通气。①对照组(8只):大鼠气管插管后自主呼吸;②机械通气组:对大鼠采用压力控制通气模式机械通气,根据气道压力水平再分10、20、30 cmH2O 3个亚组,每个亚组8只大鼠,机械通气6 h;③钌红干预组(8只):施加机械通气前鼠尾静脉注射瞬时感受器电位香草酸受体4型通道蛋白(transient receptorpotential vanilloid 4,TRPV4)非特异性阻断剂钌红(ruthenium red,RR)进行预处理;④4α-PDD干预组(8只):机械通气前鼠尾静脉注射4-α-佛波醇-12,13-二癸酸(4-α-Phorbol-12,13-didecanoate,4α-PDD)进行预处理。实验完毕后收集大鼠支气管肺泡灌洗液(BALF)和肺组织标本。采用ELISA法检测BALF中MUC5AC蛋白含量,RT-PCR法检测大鼠肺组织MUC5ACmRNA的表达水平。结果与对照组相比,机械通气组MUC5AC在蛋白及转录水平表达均增加,呈压力依赖性。30 cmH2O亚组MUC5AC蛋白及mRNA转录水平分别为[(0.71±0.10)、(6.23±0.54)]明显高于对照组[(0.29±0.05)、(1.68±0.35)](P<0.01)。在30 cmH2 O压力水平下MUC5AC的表达增加可被RR干预减弱[(0.41±0.06)、(4.15±0.22)](P<0.05),被4α-PDD干预增强[(1.12±0.09)、(8.47±0.35)](P<0.05)。结论 机械通气产生的气道压力可以通过作用于TRPV4诱导MUC5AC表达增加,这可能是压力诱导气道黏液高分泌的调节机制之一。Objective To identify the effect of high airway pressure caused by mechanical ventilation on the airway mucous hypersecretion in rats.Methods Forty-eight Sprague-Dawley rats were randomly divided into four groups.After anesthesia and tracheotomy were performed,all rats were challenged with tracheal cannula and received ventilation with small animal ventilator.Control group kept spontaneous breath without mechanical ventilation.Mechanical ventilation group were divided to 10,20 and 30 cmH2O airway pressure levels（n=8 for each level） and respectively ventilated for 6 h.Ruthenium red（RR） pre-treatment group were injected with RR via tail vein,an antagonist of transient receptor potential vanilloid 4（TRPV4） before ventilation.4-α-Phorbol-12,13-didecanoate（4α-PDD） pre-treatment group were injected with 4α-PDD,an agonist of TRPV4 before ventilation.Rats were sacrificed after ventilation,and their bronchoalvelar lavage fluid（BALF） and lung tissue were collected and stored with common methods.The mucin（MUC） 5AC MUC5AC protein in the BALF was detected by enzyme-linked immunosorbent assay（ELISA）,and its mRNA level in the lung tissues was analyzed by RT-PCR.Results Compared with control group,the expression of MUC5AC protein and mRNA were increased in mechanical ventilation group in a pressure-dependent manner,and significantly higher in 30 cmH2O airway pressure level than in control group（0.71±0.10 and 6.23±0.54 vs 0.29±0.05 and 1.68±0.35,P〈0.01）.Pretreatment of RR resulted in significantly decreased expression of MUC5AC at protein and mRNA levels in 30 cmH2O airway pressure level（0.41±0.06 and 4.15±0.22,P〈0.05）,but these events were strongly reversed by pretreatment of 4α-PDD（1.12±0.09 and 8.47±0.35,P〈0.05）.Conclusion High airway pressure induced by mechanical ventilation can significantly up-regulate MUC5AC at protein and mRNA levels through TRPV4-medicated signal pathway.

关 键 词：黏蛋白类 机械通气 瞬时感受器电位香草酸受体4 气道 大鼠 

分 类 号：R-332[医药卫生] R332.2