| The acute respiratory distress syndrome(ARDS) describes an overwhelming inflammatory reaction within the pulmonary parenchyma leading to life-threatening disturbances in pulmonary vasomotion, alveolar ventilation, and gas exchange. The early phase of ARDS is termed acute lung injury(ALI). Despite numerous efforts to develop causative or symptomatic treatment options, ARDS still has a high mortality rate of about 40-50%. Therefore there is a need for alternative therapeutic interventions. In the part I of this study, we evaluate the therapeutic effect to intratracheal administration of pulmonary surfactant(PS) and/or dexamethasone(Dex) on a rat model of early-stage ALI caused by the intratracheal injection of endotoxin. We estimate the degree of lung damage with arterial blood gas, survival, appearance and pathological structure of lungs, lung index(LI) and the total protein(TP)in the bronchoalveoar lavage fluid(BALF). The counts of WBC and the concentration of TNF-a in the BALF was measured as the sign of inflammatory. Moreover we also made a preliminary discussion about its mechanism.Firstly, we studied the right dose of endotoxin to model ALI in rats. Eschericia coli endotoxin was injected into the tracheas of anesthetize rats, arterial blood gases were determined every 2h. At the end of the experiment(i.e., 6h after the endotoxin administration), survival, lung index, total protein content, WBC counts and TNF-a in BALF were assessed. Postmortem histology was then examined. The results showed that when the rats were injected into the trachea with 1.5mg/kg(2ml/kg) endotoxin, PaO2 declined <60mmHg in 4 to 10h. At necropsy, There was obvious lung bleed, edema, and much higher in the lung index, the total protein, the WBC quantity and the content of TNF-a in BALF than that of the control group. All these achieve the standard of ALI, and the rats can survive basically for 6h that meets the requirement to observe the therapeutic effect.Then we evaluated the effect of PS replacement alone on ALI induced by intratracheal injection of endotoxin in rats. 30 mins after the beginning of endotoxin infusion, rats were divided randomly into low-doses group (100mg/kg PS), medium-doses group (150mg/kg PS), high-doses group (200mg/kg PS) and control group, given three doses ofPS and corresponding quantity of saline by instillation into the airway. All rats were studied for 6 hrs, Parameters to be measured were similar to model replication. PS treatment resulted in an improved survival and in a significantly decreased lung index and total protein in BALF. Midium and high doses of PS treatment significantly increased oxygenation 6hr after instillation when compared with the control group. Compared with the control group, the WBC counts in BALF were about tripled in three surfactant groups. Only high dose of PS treatment led to significant decrease of TNF-a in BALF. The histologic appearance of the lungs was markedly better in the groups treated with surfactant. In conclusion, surfactant alone can alleviates lung damage after endotoxin induced lung injury in the rat, but has a more limited effect on pulmonary inflammation.We also evaluated the effect of Dex treatment alone on ALL 30 mins after the beginning of endotoxin infusion, rats were divided randomly into low-doses group (0.5mg/kg Dex), medium-doses group (2.5mg/kg Dex), high-doses group (5mg/kg Dex) and control group(corresponding quantity of saline). All rats were studied for 6 hrs, Parameters to be measured were similar to model replication. The results showed that WBC and TNF-a content in BALF were decreased significantly in the rats treated with all doses of Dex compared with control rats. But Dex treatment could not improve survival and only high dose group improvedoxygenation and decreased total protein in BALF. Results suggest that Dex alone ameliorates lung inflammation greatly, but has a moderate effect on alleviating lung damage after endotoxin-induced lung injury.Lastly, We evaluated the effect of the combined administration of PS and Dex on ALL 30 mins after the beginning of endotoxin infusion, rats were divided randomly into low-doses group (PS100/Dex0.5mg/kg), medium-doses group (PS150/Dex2.5mg/kg), high-doses group (PS200/ Dex5mg/kg) and control group (corresponding quantity of saline). All rats were studied for 6 hrs, Parameters to be measured were similar to model replication. The results showed that the combined administration of PS and Dex significantly improved gas exchange, ameliorates lung inflammation, and alleviates lung damage, and these improvement were greater and longer than PS or Dex treatment alone. Based on these observations, it seems that there is an additive effect when combined administration of intratracheal PS and Dex.In part I of this experiment, an interesting finding was obtained. We found that intratracheal administration of our PS resulted in a significantly increase of WBC counts in BALF in ALI rats. In the second part, our interest was focused on whether natural surfactant instillation increased the number of diapedesised leukocytes in the alveolus, and the increased neutrophils were attributed, at least partly, to the chemotaxis of surfactant. Firstly, We administrated intratracheally 150mg/kg PS in rats... |
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