基因转染Gβγ亚基抑制剂对哮喘小鼠β受体水平和环磷酸腺苷的影响

Effect of gene transfer of G-protein beta gamma subunit inhibitor on pulmonary β-adrenergic receptor signaling and cAMP in asthma rats

目的研究基因转染Gβγ亚基抑制剂对哮喘小鼠β受体水平和环磷酸腺苷(cAMP)的影响。方法建立哮喘小鼠动物模型,经尾静脉注射转染携有Gβγ亚基抑制剂基因(βARKct)的表达质粒。用Westernblot检测基因表达。放免法检测小鼠肺部的β受体和cAMP的水平。结果(1)哮喘小鼠β受体和cAMP水平均比正常对照组明显下降(P<0.05)。(2)βARKct在经基因转染7d后的小鼠肺部有表达。(3)βARKct转染后肺部β受体的数目和cAMP受体水平均比空载质粒转染组显著上调(P<0.05)。结论基因转染βARKct对哮喘小鼠β受体和cAMP的下降有抑制作用。

Objective To investige the effects of the gene delivery of a peptide inhibitor of G-protein beta gamma subunit (Gβγ) on β 2-adrenergic receptor (βAR) and cAMP in asthmatic mice.Methods An asthmatic model was established and PcDNA-β ARKct was delivered into mice lung through intravenous injection.The protein immunoblotting was used to detect the expression of βARKct in the lungs and the changes of βAR and cAMP were evaluated by radioimmunology.Results (1)βAR and cAMP were down-regulated in the asthmatic mice.There were significant differences of those responding indeces between the asthmatic mice and control group(P<0.05).(2)The expression of βARKct in the lungs was detectable in the lungs of mice delivered β ARKct on the 7th day.(3)βAR and cAMP were up-regulated in the lungs of asthmatic mice treated with gene transfer βARKct,which were significantly different from those of asthmatic mice treated with plasmid-pcDNA3.1(P<0.05).Conclusion Gene transfer β-ARKct delivered to the lungs of asthmatic mice could up-regulate the levels of βAR and cAMP.