| Melatonin is synthesized by the pineal gland of verbebrates. Recent studies show that melatonin has anti-inflammatory, immunoregulatory, and free radical scavenging effects. It has been testified that both cytokines and free radicals induced the onset and development of immunologic liver injury(ILI) .In this paper, ILI model induced by Bacillus Calmette Guerin(BCG) & lipopolysaccharide (LPS) was established. The dynamic change and interaction between cytokines(CKs) and free radicals(FRs) were investigated by different methods, as well as the prophylactic effects of melatonin on mice ILI were studied. The results were as follows.1 .Establishment and profile of ILI modelAfter the immune response was enhanced by LPS, mice were sacrificed at different time.It was found that the activities of alanine aminotransferase (ALT) and aspartate aminotransferase(AST ) in plasma began to increase at 0.5h after tail vein injection of LPS , the peak value was at 16h.Activated oxygen(AO) unit began to increase at 0.5h and peaked at 2h and then stayed in high level with a little fluctation. The malondiadehyde(MDA) content of liver homogenate increased continuously acompanying with the activity of superoxide dismutase (SOD) decreased.The level of nitric oxide(NO) in plasma and liver homogenate began to rise from 0.5h and peaked at 16h. At the same time, the activity of tumor necrosis factor alpha (TNF- a )in plasma and liver homogenate increased dramatically in 2h. The peak value of interleukin-l(IL-l) in plasma and liver homogenate was at Ih and 4h each. Pathological examination showed that the congestion of hepatic vessel extensively was seen at 0.5hafter LPS injection, especially in portal area and centric veins. However the immigration of inflammatory cells was not observed. Then hepatic dot necrosis were scattered and inflammatory cells appeared around the necrotic hepatocytes,which was aggravated gradually at 2h,4h,8h,with the changes from dot-forcal necrosis to bridging necrosis and inflammatory cells immigrated extensively. At 16h after LPS injection, striped necrosis, bridging necrosis and congestion in liver sinusoids were significant with scattering immersion of inflammatory cells. With the time on the degree of liver injury was attenuated while dot-necrosis still lasted 24h.2. Prophylactic effects of melatonin on mice ILIBoth melatonin (0.25,l,4mg ?kg-1) and bifendate were found to significantly decrease the serum transaminase (ALT,AST) activities in ILI mice. Meanwhile, melatonin decreased AO, MDA content and increased SOD level in liver homogenate. Furthermore, melatonin significantly reduced TNF- a , NO and IL-1 production in serum. Bifendate significantly reduced MDA and IL-1 while had little effect on the other indexes such as AO, SOD and TNF- a . It was found that melatonin and bifendate were able to attenuate the area and extent of necrosis, reduce the immigration of inflammatory cells.3. Effect of melatonin on the function of hepatocytes(HC) and kupffer cell(KC)HC at different concentrationsOO^lO'^O'^lO^lO^mol ?L'1) and dexamethasone (10~8mol ?L~!)were incubated with melatonin in vitro for 48h. The proliferation of HC and the releasing of lactic dehydrogenase( LDH) were not changed significantly. Melatonin at the concentrations of 10~8~10~6 mol ?L"1 were able to inhibit directly the production of TNF- a while could decrease IL-1 production only at the concentrations of 10~6 mol ?L"1 of KC induced by LPS. Melatonin has no effect on NO production. Dexamethasone significantly decreased TNF- a ,NO and IL-1 production. HC incubatedwith BCG-induced KC and LPS was added. It was found that the activities of ALT , LDH, TNF- a , IL-1,NO and MDA in supernatant were significantly increased. Melatonin had little effect on the level of ALT, LDH and NO in median , but melatonin at the concentrations of 10~7~10~5 mol - L-1 reduced the content of TNF- a and MDA while concentrations of 10"6~10~5 mol - L-1 decreased the content of IL-1. Dexamethasone significantly reduced the content of TNF-a ,NO and I... |
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