| Immune-mediated liver injuries are involved in the pathogenesis of many liver diseases. Concanavalin A-induced hepatitis, CIH, is one of the typical models for research of mechanism and drug development of immune mediated liver injury.Lipoxins, LXs, metabolites produced from arachidonic acid by lipoxygenase, have dual anti-inflammatory and pro-resolution activities. Recently, it also found that LXs also regulate the immune response. But the life of native LXs are too short to be convenient for research and utilization. So the analogs are artificially produced by modification of the structure of native LXs, which caontain the functions of native LXs. BML-111 is an artifical agonist of lipoxin receptor, maintaining the essential groups for the function of LXA4. Experiments in vivo and in vitro had proved the multiple bioactivities of BML-111. But there is no report that whether it is also effective in immune-mediated liver injury.The aims of the present study are:by constructing the CIH model, to study the protective effect of BML-111 on the liver injury of CIH, to explore the possible mechanism of its protective effect.To investigate the protective effect of BML-111 on CIH, BML-111 (1μg/g) was adiministered i.p. about 30min before ConA injection i.v (generally 15μg/g without special indication), another three groups of PBS, BML-111, and ConA were used as controls. Resultes:compared with the group of ConA, the serum ALT activity was significantly decreased in BML-111 treating group. H&E staing showed that there are massive cell death areas in the group of ConA, companying with extensive denaturation of hepatocytes, filtration of RBC and leucocytes. But in the BML-111 treating group, the major tissue damage was denaturation of hepatocytes, with spots of cell death and filtration of RBC and leucocytes. TUNEL staining also showed that, compared with the groups of single ConA, BML-111 treating significantly decreased the cell death. And the survival test under the charge of half-lethal ConA (25μg/g) showed that, compared with the groups of ConA, BML-111 treating group significantly promoted the survival of animals. Conclusion: BML-111 could significantly decrease the liver injury caused by ConA.The groups were devided as the same as before-mentioned. Results:compared with the group of ConA, BML-111 significantly increased the total SOD activity and MPO activity, and decreased MDA of the homogenate of liver, BML-111 also inhibited the activity of NF-κB, and decreased the level of TNF-a in the serum, but it had no influence on the level of IFN-y in the serum, and could not change the infiltration and activation of lymphocytes in the liver. Conclusion:BML-111 had the ability of anti-oxydative damage, decreased the infiltration of neutrophils, and inhibited the activation of NF-κB and release of TNF-α. BML-111 had no influence on the release of IFN-y, lymphocytes infiltration and activation in the liver.Groups:Blank, BML-111 (1μg/ml), ConA (10μg/ml for macrophage,5μg/ml for splenic T cell), BML-111+ConA. Results:compared with ConA, BML-111 decreased the level of TNF-a and Rantes in the supernate of macrophage, and BML-111 had no influence on the IFN-y release and activation of splenic T cell. Conclusion:BML-111 could regulate the response of ConA in macrophage, but not in T cell.Conclusion:1. BML-111 could significantly decrease the liver injury caused by ConA.2. The protection effects of BML-111 were related with the anti-oxydative damage, decreasing the infiltration of neutrophils, and inhibiting the activation of NF-κB and releasing of TNF-α; but without the influence of on the release of IFN-y, lymphocytes infiltration and activation in the liver.3. Experiments in vitro furtherly testified that BML-111 can regulate the response of ConA in macrophage, but not in T cell. |
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