Studies On The Mechanism Of AQP-1 Changes In Endotoxin-induced Acute Lung Injury In Rabbits

Objective: Acute lung injury(ALI) is one of clinical severe diseases whichhas high mortality. Gram-negative bacteria infection is the most frequently causative factor. The most active element of Gram-negative bacteria is endotoxin(ET). ET which chemical element is lipopolysaccharide(LPS) can make injury to lung and other organs. In our study we want to reproduce ALI animal models in rabbits by intravenous injection of ET and examine the changes of von Willebrand factor(vWF), neutrophil elastase(NE), malondialdehyde(MDA), and superoxide dismutase(SOD), aquaporin-(?)(AQP-(?)) and others. The animals were treated with chloroquine after intravenous injection of ET. The purpose of our study is to investgate the etiopathogenesis of ALI induced by ET and to find out effective therapeutic method for ALI in the clinic.Methods: 24 flap-eared white rabbits were randomly assigned to threegroups: control group(group A), injury group(group B) and therapeutic group(group C). The rabbits of group A were intravenously injected with normal saline. The rabbits of group B were intravenously injected with ET(600ug/kg) one time so as to induce animal models of ALI. In group C ainimals were treated by intravenously one injection of chloroquine(5mg/kg) after ET(600ug/kg) injection. The vital signes such as respiratory rate(RR), heart rate(HR) and blood pressure(BP) were monitored and recorded. Before the experiment(Oh) and after experiment of 0.5h, 1h, 2h, 4h, 2.5ml arterial samples were drawn respectively for examining vWF, NE, MDA, SOD activity and blood gas analysis. The rabbits were killed immediately after 4h experiment. Pathological changes of lung tissues were observed and immunohistochemical expression of AQP-1 in right lungtissues were examined by simiquantitative analysis of average gray level. Wet/dry ratio of left lung was mesaured carefully. The statistical analyses were made with the help of SPSS 13.0 statistical software.Results: Compared with group A, the animals in group B changed in manyaspects. Increased RR especially at 0.5h was found after experiment. BP was decreased persistently and reached to 58.78mmHg at 4h. HR imcreased at 0.5h and then gradually solwed down to the baseline. Aterial blood partial pressure and oxygenation indexes were significantly decreased at 0.5h, which was 54.65mmHg and 259.71mmHg respectively. The pH value was decreased markedly after ET injection and it went to 7.185 at 4h. The content of vWF, NE, and MDA was significantly increased, while SOD was markedly decreased. Histopathological examination showed that in group B we could find microvascular injury, microcirculation disfuction, white cell sequestration, microthrombosis, pulmonary edema, increased pulmonary wet/dry ratio and so forth. AQP-1 expression of immunohistochemical photograph in group B was weaker than that in group A. The results in group C were similar to those in group B, but the changes of tendency were obviously lighter than those in group B.Conclusion: The results in this experiment made known that one time intravenous injection of exdotoxin(600ug/kg) was able to reproduce early ALI model in rabbits. Increased vWF, high activity of NE and decreased expression of AQP-1 had something to do with devlopment of ALI. Oxidative stress reaction and PLA₂ reactivation mihgt play important role in the pathogenesis of ALI. The cholroquine of PLA₂ inhibitor had some protective effects to ALI induced by ET in rabbits.