| Objective: Use rhBNP to intervention endotoxin-induced acute lung injury in dogsand explain the protective effect on the lung in the view of oxidation-antioxidation.Methods:1.Establishment of acute lung injury dog models. Choose20healthyadult dogs (14.2±0.38) kg. And then they were randomly divided into four groups:control group (group A), acute lung injury group (B), acute lung injury+the low doseof rhBNP group (C group), acute lung injury+the high dose of rhBNP group (GroupD).Use2%sodium pentobarbital30mg/kg for intravenous anesthesia. In the experiment,sodium pentobarbital was continuous intravenous infusion with l0mg kg-1h-1tomaintain. Supine position was fixed, orotracheal intubation connections mechanicalventilation. Keep respiratory rate f18beats/min and tidal volume Vt10ml/kg. Rightinternal jugular vein puncture and the right femoral artery puncture in dogs, catheter.The catheter sheath side of the tube connected to the PiCCO temperature probe, and theright femoral artery catheter connected PICCO monitor. Except the group A, the otherthree groups were induced using1mg/kg LPS (diluted in20ml saline,2ml/min)infused in10minutes by the central vein. Monitoring of arterial blood gas.During theexperiment, four groups were given the balanced salt solution and the progress of10ml/h/kg conducted infusion.2. The drug delivery methods and indicators formonitoring. On the basis of successful models, normal control group (group A, n=5)was given the same amount of normal saline. ALI group (group B, n=5) was given LPS1mg/kg and the same amount of normal saline. rhBNP low dose group (group C, n=5)was given LPS1mg/kg and rhBNP5μg/kg. rhBNP high dose group (group D, n=5) wasgiven LPS1mg/kg and rhBNP10μg/kg. Recorded the animal’s vital signs of each groupat the time of0h,2h,4h,8h,12h. At the same time, we collected arterial blood for bloodgas analysis to determination of PaO2as recording oxygenation index. Use the PiCCO monitoring technology for extravascular lung water (EVLW) and pulmonary vascularpermeability index (PVPI) at each time point. After12h of the experiment, kill the dogs.Part of the lung tissue was used to measured W/D ratio. Another part of the lung tissuewas used for HE staining and observed the histopathology through light microscopy.Determine MPO activity and MDA levels of the lung tissue.Results:1.The results of W/D and HE staining of lung tissue showed that low-dose of rhBNP group (C) and high-dose of rhBNP group (D) reduce the degree ofpulmonary edema; alveolar congestion and bleeding can also be improved. Theimprovement of high-dose of rhBNP (group D) is much more obvious.2.The blood gasresults: both low-dose of rhBNP group (C) and rhBNP in high-dose group (D) canincrease partial pressure of oxygen obviously. And the oxygenation index has beenfurther improved. PiCCO monitoring results also showed that the extravascular lungwater drop and the capillary permeability can be improved. The improvement of high-dose of rhBNP (group D) is much more obvious.3.In the process of acute lung injury,oxidative stress injury is serious. The intervention by using rhBNP decreased theexpression levels of MPO and MDA significantly and reduced the oxidative stressinjury.Conclusion:1. rhBNP can mitigate the damage of lung tissue, improve its functionand tissue oxygenation,reduce extravascular lung water and capillary permeability index.Its role has the dose-effect relationship.2. rhBNP can improve antioxidant enzymeactivities of the lung tissue which suggests that part of the mechanism of acute lunginjury in animal protection is achieved by regulating the endogenous antioxidantenzyme activity. |
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