甲型流感病毒对于在体大鼠肺泡上皮液体清除的影响

The Influence of Influenza Virus A on Alveolar Fluid Clearance in Rat Lungs

目的探讨甲型流感病毒(A/PR/8/34株,H1N1)对在体大鼠肺泡液体清除率(AFC)的影响,以及β1-肾上腺素能受体激动剂地诺帕明对于在体大鼠AFC的影响机制。方法将SD大鼠分为正常对照组、H1N1感染模型组、感染后地诺帕明干预组。研究H1N1感染后AFC的变化以及地诺帕明的调节作用,并应用ELISA方法检测肺组织内环腺苷酸(cAMP)、环鸟苷酸(cGMP)的水平。结果正常对照组AFC为(17.25±1.01)%,肺干湿重比(W/D)为4.99±0.02;H1N1感染组AFC降为(9.15±1.01)%,W/D升高至6.77±0.13。干预组可以显著地提高H1N1感染后的AFC[(14.41±1.41)%],W/D为5.98±0.22。正常肺组织内cAMP活性为(2.73±0.06)nmol·mg-1·mg-1,cGMP的活性为(5.10±1.88)pmol·mg-1·mg-1。H1N1感染组肺组织内的cAMP明显下降[(1.43±0.06)nmol·mg-1·mg-1],cGMP水平升高[(7.34±0.40)pmol·mg-1·mg-1],应用地诺帕明可以提高肺组织内的cAMP的活性[(2.06±0.16)nmol·mg-·1mg-1],cGMP的活性下降为[(6.16±1.36)pmol·mg-·1mg-1]。结论 H1N1感染可导致大鼠AFC明显下降、肺水肿加重。地诺帕明可以提高在体H1N1感染大鼠模型的AFC、减轻肺水肿,并可以逆转感染组cAMP/cGMP的下降。说明β1-肾上腺素能受体激动剂提高AFC及减低肺水肿可能是通过cAMP-PKA信号转导途径完成。

Objective To investigate the influence of influenza virus A（H1N1,A/PR/8/34 strain）on alveolar fluid clearance（AFC）in vivo and the effects of β1-adrenergic agonist on AFC in rat lungs infected by H1N1.Methods Fortyfive rats were divided into control group（n =12）,H1N1 infection group（the rats were infected with influenza virus strain A/PR/8/34,n =18）,β1-adrenergic agonist groups（the rats were administrated with β1-adrenergic agonist after HIN1 infection,n =15）.AFC was estimated by the progressive increase in the albumin concentration over 30 minutes.The activity of cAMP and cGMP in the lung tissues of control,H1N1 infection and β1-adrenergic agonist groups was measured.Results The infection with H1N1 resulted in a decline in AFC 9.15±1.01% vs control group 17.25±1.01% and increased lung water content（W/D was 6.77±0.13 vs control group 4.99±0.02）.H1N1-mediated inhibition of AFC could be reversed to 14.41±1.41% by the administration of β1-adrenergic agonist denopamine.H1N1 infection increased cGMP levels 7.34±0.40 pmol·mg-1· mg-1 vs control group 5.10±1.88 pmol·mg-1·mg-1 and decreased cAMP levels 1.43±0.06 nmol·mg-1·mg-1 in lung tissues compared with control group.β1-agonist denopamine reversed the level of cAMP to 2.06±0.16 nmol·mg-1·mg-1 and cGMP to 6.16±1.36 pmol·mg-1·mg-1.Conclusion H1N1 infection decreased AFC and increased lung edema.β1-agonist denopamine could reverse AFC and the ratio of cAMP/cGMP in H1N1 infected lung tissues.β1-agonist might regulate AFC through the pathway of cAMP-PKA.