| BACKGROUNDThe pathological characteristic of acute lung injury(ALI) is diffused alveolar-capilary membrane injury ,which were caused by severe infection,trauma,shock,et al.The severe stage is acute respiratory distress syndrome(ARDS),the clinical situation is respiratory distress and intractable hypoxemia. The pathogenesis is very complicated ,it is still not clear although many studies have been done.Recently the attention was paid to inflammatory response,and it is regarded that ALI is the result of uncontrolled inflammatory response in the lung due to various causes.It is the pulmonary menifestation of systemic inflammatory response. . There are many effector cells , cytokines and adhension molecules to participate in this disease.It is belief to block or lessen inflammatory casecade can prevent the development of ALI successfully.Chinese traditional medicine colquhounia root tablets were purified from colquhounia root by moden pharmaceutical product technology.It was confimed that favourable anti- inflammatory effects by experimental studies and clinical application.But wheather it has the same effect on acute lung injury is not very clear.In this experiment ,rats were treated with colquhounia root tablets during the establishment of the models of ALI,we were to investigate its effects on the ALI and the mechanisms for applying theoretical evidence to treat ALI with colquhounia root tablets in clinic practice.METHODS1.36 healty Wistar rats weighing 200-250g,were randomly divided into three groups:the control group,the ALI model group and the colquhounia root treated group. In ALI group oleic acid 0.04ml.kg-1 was injected into trail vein to establish ALI models,in colquhounia root tablet treated group colquhounia root tablet with 600mg.kg-1 day-1 were instilled into the stomach of each Wistar rat for ten consecutive days before intravenous injection of same dose oleic acid,in control group same dose saline was injected. After 4h of establishing model,all animals were sacrificed.2.Total superoxide dismutase (SOD) level of the plasma and broncho-alveolar lavage fluid (BALF) were measured by the nitrite method, glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) activities were detected by 5,5'-dithionbis (2-nitrobenzoic acid) and whist thiobarbituric acid colorimrtric method respectively.3.Lung wet/dry ratio, lung permeability index (LPI) ,WBC number and percentage of active neutrophils in BALF were counted .Morphologic lung changes in the three groups were observed at both light and electron microscopic levels.4.The positive expression of Nuclear factor-κB and tumor necrosis-αwereperformed in the lung tissue by SABC in three groups.5.The positive expression of intercellular adhension molecule-1 in lung tissues by SP and CD11a,CD11band CD18 in neutrophil were quantitatively analyzed by flow cytometry using monoclonal antibodies in three groupsbbb.RESULT1. Effects of colquhounia root on pathologic changes of ALI in rats1.1 Light microscope(HE): Alveoli appeared normal in the size and shape in the control group.,In the ALI group there were multiple lesions,including local hemorrhage ,diffuse sever congestion and edema in the interstitiun and alveoli with infiltration. of red cells, many inflammatory cell into the alveolar lumen and thickening of alveolar walls.The microscopic lesions observed in the colquhounia root treated group were lighter than the ones in the ALI group .The changes were localized.1.2 Electron microscope: The pulmonary microvascular basement membrane and endothelial cells in the control group were normal. While in the ALI group, the pulmonary microvascular basement membrane defect and puff , endothelial cells edema seriously and not integral. The pulmonary microvascular basement membrane was integral relatively,endothelial cells mild edema in the colquhounia root treated group .2. Effects of colquhounia root on level of GSH-Px,MDA and SOD in plasma and BALF of ALI in ratsThe activies of SOD and GSH-Px in the ALI group in plasma and BALF deceased significantly compared with the control group(P<0.01). in the treated group, the activies of SOD and GSH-Px in plasma and BALF increased significantly compared with the ALI group(P<0.01), but higher than that in the control group (P<0.05).The content of MDA in the ALI group in plasma and BALF increased significantly compared with the control group(P<0.01), in the treated group, the content of MDA in the ALI group in plasma and BALF deceased significantly compared with the ALI group, but lowerr than that in the control group (P<0.05).3. Effects of colquhounia root on W/D,LPI ,WBC number and percentage of neutrophils in BALF of ALI in ratsW/D,LPI ,WBC number and percentage of neutrophils in the ALI group increased significantly compared with the control group(P<0.01).In the treated group , W/D,LPI ,WBC number and percentage of neutrophils deceased significantly compared with the ALI group(P<0.01),but except the LPI,the others higher than that in the control group (P<0.05).4. Effects of colquhounia root on expression of NF-κB and TNF-αin lung tissues of ALI in ratsThe expression of NF-κB and TNF-αin the ALI group increased significantly compared with the control group(P<0.01).In the treated group , The expression of NF-κB and TNF-αdeceased significantly compared with the ALI group(P<0.01),but higher than that in the control group (P<0.05).5. Effects of colquhounia root on expression of ICAM-1 in lung tissues and CD11a,CD11b and CD18 in neutrophil of ALI in ratsThe expression of ICAM-1 and CD11a,CD11b and CD18 in the ALI group increased significantly compared with the control group(P<0.01).In the treated group , The expression of The expression of ICAM-1 and CD11a,CD11b and CD18 deceased significantly compared with the ALI group(P<0.01),but higher than that in the control group (P<0.05).CONCLUSION1. There is significant diorder of oxidant and antioxidant in the lung tissue of oleic acid induced ALI in rats.2. Colquhounia root can alleviate the pathological injury of the lung of oleic acid induced ALI in rats ,It can balance the disorder of oxidant and antioxidant.3. Colquhounia root can lessen the degree of lung inflammatory by inhibiting the over activition of NF-κB and TNF-αin lung tissues4. Colquhounia root can reduce activition and aggregation of PMNs by downregulation the expression of ICAM-1 and CD11a,CD11b and CD18 .
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