| Objective: Acute lung injury(ALI) is a common seen critical disease in the clinic.The pathogenesis of it is not clear yet;It's mortality is high,and it is difficult to cure of.ALI is caused by many basic illness,endotoxemia caused by Gram negative(G) bacterium is the most common one among them.In this study the ALI animal models were replicated by intravascular injection of endotoxin(ET) to the flap-eared white rabbits at a time.The possible machanisms of cyclooxygenase-2 (COX-2),oxide stress,inflammation beyond control,expression of COX-2mRNA and microvascular disorder in ALI' pathogenesis were studied. Correlative marks of physiology,biochemistry and pathology were observed or measured during and after experiment.And the influence of ALI on the animals'heart were observed also.Naproxen were given to rabbits so as to study the antagonistic effects of naproxen on the ALI animal model induced by ET.Methods: 24 flap-eared white rabbits were randomly assigned to three groupsrcontrol group(group A), ET-treated group(group B) and combination group (treated by ET and naproxen, group C).There were eight animals in each group. The animal model of ALI was induced by intravenous injection of ET(600μg/kg) through jugular vein at a time. Five minutes ahead of injection of ET,naproxen(50mg/kg)were injected intravascularly to rabbits in group C,and the normal saline were given to rabbits in group A.During the experiment, arterial blood pressure(BP), respiratory rate(RR),and heart rate(HR) were monitored by means of Hewlett Packard monitor.Arterial gases were measured at the same time. Contents of thromboxane B2(TXB2), 6-keto-prostagIandin F1α(6-keto-PGF1α), endothelin-l(ET-l) and activities of angiotesin-converting enzyme(ACE) in serum were measured before andduring the experiment at 30,60,150,240 minutes. Contents of interleukin-lO(IL-lO) and interleukin-19(IL-19) were measured before and after experiment.Rabbits were killed at 240min of the experiment.Contents of TXB2, 6-keto-PGia,ET-l,IL-10,IL-19,maleic dialdehyde (MDA) and activities of superoxide dismutase(SOD) were measured in the lung tissues.Contents of TXB2,6-keto-PGia and Heart-fatty acid binding protein(H-FABP) in heart tissues were also measured.The pathologic changes of pulmonary tissues and heart tissues were examined with light microscope.Peroxisome proliferator-activated receptor-y (PPARy) were examined by immunohistochemistry in lung tissues. Expression of COX-2mRNA were examined by RT-PCR.The left lung were used to measure the ratio of wet/dry.Results: RR of rabbits of group B was significantly increased after ET injection,but it was not clearly changed in group A;HR, BP and PaO2 in group B were significantly lower than those in group A.The changes above in group C were similar to those in group A.During the experiment,contents of TXB2,6-keto-PGia, ET-1 were signicantly increased in group B.After experiment in 30 minutes serum ACE activities were significantly higer than it in group A,and ACE activities in group C were kept at a lower level.In group B,contents of TXB2, 6-keto-PGia,ET-l, MDA,IL-10,IL-19 increased signicantly in lung tissues and SOD activites decreased compared to those seen in group A.In group C,those changes were almost similar to group A.Contents of IL-19 and MDA in group C were higher than those in group A.Typical inflammatory pathological changes could be seen in group B easily.Pulmonary tissues injuries in group C were not severe than those in group B. PPARy was decreased in lung tissues of group B and C compared to it in group A. Expression of COX-2 mRNA increased in lung tissues of group B and C,which were signicantly higher than group A.Heart histopathologic injuries in group B were clearly observed,but no changes were observed ingroup A.The heart injuries were not severe in group C compared with group B.Conclusion: (Dlntrovenous injection of ET at a time can successfully replicated ALI animal model in rabbits.?COX-2 activities in both serum and lung tissues and expression of COX-2 mRNA in lung tissues were increased notably in ALI animal models.(3)Oxidative stress injury and the relative deficiency of anti-oxidative stress abilities was one of pathagenesis of ALI.@IL-10 and IL-19 in both serum and lung tissues were excessfully released in animal models of ALI. ?Pulmonary microcirculation disorders was one of the pathaphysiological changes in ALI.(6)PPARy expression in lung tissues was decreased in group B.?Naproxen had some therapeutic effects on ALI induced by ET,which effects were the follows,sach as antaginizing COX-2 activity and activing PPARy.(§)The rabbits' heart were also injuried after intravenous injection of ET. |
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