The Investigation Of Expression Of Caveolin-1in Relation To Downstream Signaling On The Effects Of Lung Injury In Rats Ventilated

Objective: We will observe expression of caveolin-1(cav-1) and theactivation of downstream endothelial nitric oxide synthase (eNOS) mediated bycav-1, and also the inflammatory response mediated by these signal. Throughthis investigation, we try to build up the exact mechanism about caveolin-1withits downstream signal regulating lung injury induced by mechanical ventilationand provides a new theoretical mechanisms for lung injury prevention.Methods: Forty healthy male SD rats were randomly assigned into5groups(n=8each) according to the tidal volume (Vt), respiratory rate(RR) andduration of mechanical ventilation: group A spontaneous breathing; groupB1,B2(Vt6ml/kg, RR60bpm, I:E1:2,duration1h,2h); group Cl,C2(Vt30ml/kg,RR40bpm, I:E1:2,duration1h,2h). After maintaining ventilation for1h or2h,all rats were sacrificed and specimens of lung tissues and bronchoalveolarlavage fluid (BALF) were harvested. Lung pathological changes were observedby microscopy and diffuse alveolar damage (DAD) score were estimated. Theprotein levels of cav-1, eNOS, interleukin-1receptor-associated kinase4(IRAK4)and nuclear factor-kappaB (NF-κB) p65in lung tissues were assayed withimmunohistochemistry staining. The expression levels of cav-1,eNOSmRNA in lung tissue were measured by reverse transcription-polymerase chain reaction(RT-PCR).Lung myeloperoxidase(MPO) activity were measured by colorimetricanalysis, wet-dry weight ratio (W/D) were measured. The levels of tumornecrosis factor-α(TNF-α) in BALF were measured by enzyme-linkedimmunosorbent assay(ELISA). Hemodynamic parameters were measuredthroughout the study period. Arterial blood gases were measured every one hour.Results: There were no statistical significance in the expression ofcav-1,eNOSmRNA and cav-1,eNOS, IRAK4, NF-κBp65protein,as well as W/Dratio, MPO and TNF-α in BALF among group A, groupB1and groupB2.Theexpression of cav-1mRNA and cav-1, IRAK4, NF-κBp65protein weresignificantly up-regulated, the expression of eNOSmRNA and protein wassignificantly down-regulated significantly increased while W/D ratio, MPO(U/g)and TNF-α(pg/ml) in BALF were significantly increased in group C1and groupC2than in group B1and group B2accordingly(all P<0.05). With the furtherprolong the time of mechanical ventilation, each index change were moreobvious in group C2than group C1(all P<0.05). There was no significantdifference in terms of arterial blood gas analyses and mean arterial pressure(MAP) in the five groups before ventilation. PH values in arterial blood in groupC1and group C2tended to be higher, while mean arterial pressure (MAP),partial pressure of carbon dioxide in arterial blood(PaCO2) and partial pressureof oxygen in arterial blood(PaO2) were lower than in group B1and group B2accordingly after ventilation. Conclusions: cav-1and the activation of downstream signal in lung tissueparticipate in the developmemt of the ventilator-induced lung injury.