Study On Endotoxin-induced Acute Lung Injury And Therapeutic Effects Of Fructose-1, 6-diphosphate In Rabbits

OBJECTIVE: Acute lung injury (ALI) belongs to severely clinical disease rather easy to be seen, of which mortality rate gets up to about from 30 to 40 percent. Endotoxemia caused by Gram-bacteria, out of all pathogenies, is the most common reason. So, animal ALI models were replicated with E.coli endotoxin (ET) injected intravascularly at a time in flap-eared white rabbits in this study. By the methods of observing or measuring correlative marks of physiology, biochemistry and pathology within those ET-induced ALI models, pathophysiologic changes were further researched, and the possible mechanisms of a few factors resulting in pulmonary injury, such as phospholipase A₂ (PLA₂), oxidative stress, procoagulant activities and microvascular disorder, were also further studied. Meanwhile, this study explored the therapeutic effects of fructose-1,6-diphosphate(FDP) on therapeutic group, in order to further develop the clinical therapeutic method of ALI.METHODS: 24 flap-eared white rabbits were randomly assigned to three groups: control group (group A), injury group (group B) and therapeutic group (group C). There were eight animals in each group. Rabbit ALI models were replicated with intravascular ET injection (500 μ g/kg weight) at a time in group B and C, and FDP was intravascularly injected (300 μ g/kg weight) as therapeutic measure in group C. Whereas, animals of group A were used as contrast only injected with saline intravascularly. During the experimental course, respiratory rates, heart rates, blood pressures, arterial blood gases, blood cell counts and activities of PLA₂ inserum were measured at 0h, 0.5h, 2h, 4h and 6h respectively. After rabbits sacrificed at 6h, the pulmonary activities of PLA₂ and the superoxide dismutase (SOD) were measured, and pulmonary contents of lipid peroxide (LPO), thromboxane B₂ (TXB₂), 6-keto-prostaglandin F_1α (6-keto-PGF_1α) and endothelins-1 (ET-1) were detected. Then, pathologic changes of lung tissues were observed.RESULTS: Compared with group A, animals of group B showed typical characters of ALI at 0.5h after ET injected, including respiratory rates and heart rates increase, blood pressures and arterial blood oxygen pressures decrease as well as peripheral white blood cells count drop (p <0.05). The same marks of group C were similar to those of group A. In the process of this study, the serum PLA2 activities of group B were higher than those of group A (p <0.01), and persistently rose, along with which the pulmonary PLA2 activities of group B were higher than those of group A (94.69 ± 20.01 vs 44.06 ± 4.81, p <0.01). The serum and pulmonary PLA₂ activities of group C were mildly higher than those of group A and lower than those of group B. Compared with group A at 6h after ET injected, the pulmonary SOD activities were lower (563.64 ± 153.12 vs 839.90 ± 111.03, p <0.05), but, the contents of pulmonary LPO (0.1545 ± 0.0296 vs 0.1131 ± 0.0112, p <0.05) and the ratios of pulmonary TXB₂/6-keto-PGF_1α (280.63± 48.75 vs 206.08 ± 59.81, p <0.01) could be seen increasing in group R, and the pulmonary ET-1 contents of group B showed upward trend (8.0426± 2.3114 vs 6.6584 ± 1.2168, p=0.1561). However, in group C, the value of pulmonary SOD activities, LPO contents, TXB₂/6-keto-PGF_1α ratios and ET-1 contents were all close to those of group A. Typically pathological changes could be seen in group B easily. Pulmonary tissues of group C showed less injuries and similar to those of group A.CONCLUSION: â‘  ALI animal models of flap-eared white rabbits can be successfully replicated with ET injected intravascularly at a time, â‘¡ As a key enzymes of inflammatory cascade reaction, activation and continually increased activity of PLA₂ play crucial roles in the pathogenesis...