The Effect Of Alprostadil Postconditioning On Toll-like Receptor4Expression In Dogs With Hemorrhagic Shock Induced Lung Injury

Objective: To study of the influence of Toll-like receptor4and cytokines lung tussue byalprostadil and lung protection mechanisms with hemorrhagic shock in dogsMethods: Eighteen experiment dogs were randomly divided into three group(n=6),conrtol group(group C), hemorrhagic shock group(group A),alprostadil group(group B).All the dogs were anesthesitized with2.5%sodium pentobarbital (1ml/kg), then operatedendotracheal intubation. A femoral artery catheter was placed for mean arterial pressure(MAP) monitoring bloodletting and blood sampling. A femoral vein catheter was placedfor central venous pressure (CVP) monitoring and infusion the blood and givingmedici-ne,with the right thoracotmy, heparin sodium3mg/kg,the hemorrhagic shock mode wasestablished after5min. Bloodletting from the femoral artery until the blood pressure dropto405mmHg(1mmHg=0.133kPa), maintaining the blood pressure to preoperative level90min by intermittent feedback or bloodletting.only Placing a femoral artery catheter anda femoral vein catheter, not bloodletting in group C. establishing the acute lung injurymodel of hemorrhagic shock in group A, Shock90minutes after infusion of alprostadil（30ng.kg-1.min-1） in group B. Establishing the acute lung injury model of hemorrhagicshock after30min in group B.Samples of arterial blood and lung tissue were collected at T0(before shock), T1(90min after shock), and T2(2hour after recovery),T3(4hour afterrecovery). Samples of arterial blood were used to calculate oxygennation index (OI).Samples of lung tissue were collected to observe changes of pathology with light micro-scope, to measure the level of mRNA of TLR mRNA with real-time PCR. Samples ofvenous blood were collected at T0(before shock), T1(90min after shock), T2(2hour afterrecovery), T3(4hour after recovery), to measure the level of NF-κB、TNF-α、IL-1β、IL-10.Results:(1)The change of oxygennation index (OI): There were no significant differencein OI in all groups at T0(P>0.05).The OI of groups A、B was lower than that of group C atT1-T3(P<0.05),but The OI of group B was higher than that of group A(P<0.05).(2)The change of expression of TLR4mRNA in dogs lung tissue: There were nosignificant difference inTLR4mRNA in all groups at T0(P>0.05).The TLR4mRNA of groups A、B was higher than that of group C at T1-T3(P<0.05),but The TLR4mRNA ofgroup B was lower than that of group A (P<0.05).(3)The change of NF-κB、IL-1β、TNF-ɑ、IL-10in dogs serum: There were nosignificant difference in NF-κB、IL-1β、TNF-ɑ and IL-10in all groups at T0(P>0.05).TheNF-κB、IL-1β、TNF-ɑ and IL-10of groups A、B was higher than that of group C at T1-T3(P<0.05),but The NF-κB、 IL-1β、TNF-ɑ and IL-10of group B was lower than that ofgroup A (P<0.05).(4)The structure of lung tissue in optical microscope examination: The structuresof lung tissue were clearly in all groups at T0and in C groups at all times. The lung tissuewas damaged seriously in group A than that in group B at T1until T3.Conclusion:(1)The serum levels of NF-κB、IL-1β、TNF-ɑ and IL-10wereincreased,the expression of lung tissue TLR4mRNA was increased, the lung tissue may bedamaged after hemorrhagic shock.(2) Alprostadil may reduce hemorrhagic shock lung injury by decreasingTLR4mRNA gene expression, restrainning cytokines release.