哮喘豚鼠肺内ADM表达变化及对离体气管条张力的作用

CHANGE OF THE EXPRESSION OF ADRENOMEDULLIN IN LUNG AND EFFECT ON CONTRACTION OF ISOLATED TRACHEAL STRIP OF ASTHMATIC GUINEA PIGS

目的 :通过观察肾上腺髓质素 (ADM)mRNA在豚鼠哮喘模型肺内的表达及对哮喘豚鼠离体气管条张力的影响 ,研究ADM在支气管哮喘 (简称哮喘 )发病机制中的作用。方法 :用原位杂交方法检测ADMmRNA在豚鼠哮喘模型肺内的表达 ,用组胺诱导豚鼠离体气管条收缩后 ,观察不同浓度的ADM对其收缩作用影响。结果 :原位杂交结果显示正常及哮喘豚鼠肺内均有ADMmRNA的表达 ,但哮喘组较正常组明显增多 (P <0 .0 5) ,ADM可抑制组胺诱导的哮喘豚鼠离体气管条的收缩 ,并呈量效关系 ,当浓度达 1 0 - 8mol/L时抑制率达到最大 ,而且即使加大ADM的浓度 ,抑制率未继续明显增加 ,并对致敏气管螺旋条的舒张作用明显大于正常气管螺旋条。结论 :哮喘时 ,肺内ADMmRNA的表达明显增多 ,ADM可抑制组胺诱导的豚鼠离体气管条的收缩 ,浓度为 1 0 - 8mol/L时抑制率达到最大。

Aim: To study the formation and localization of ADM mRNA in lung tissues and investigate the effects of ADM on isolated tracheal strip contraction induced by histamine in athmatic guinea pig.Methods: The guinea pigs( n =22) were randomly divided into two groups of 11 each:asthmatic group and control group. The formation and localization of ADM mRMA were observed by in site hybridization.The effect of exogenous ADM on contractions of isolated tracheal strip of the asthmatic guinea pigs to histamine was examined.Results:There were strong positive expression for ADM mRNA in airway epithelial cells(AEC), smooth muscle cells(ASMC)in asthmatic group.The control group showed significantly decreased number of ADM mRNA positive cells in lung tissues.From 10 -11 mol/L to 10 -7 mol/L,ADM may cause concentration depend pentiation of the isolated tracheal strip contraction induced by histamine of athmatic group which was higher significantly compared the control group ( P <0.05).10 -8 mol/L ADM reached the maximal relaxation ,with the increasing of ADM,neither asthmatic nor control group can increase the relaxation.Conclusion:There is ADM mRNA overproduction in AEC and ASMC and exogenous ADM may inhibit isolated tracheal strip contraction induced by histamine of athmatic guinea pig,which may contribute to airway inflammation and hyperresponsiveness in asthma.