Effects And Mechnisms Of Melatonin On Immunologic Hepatic Fibrosis In Rats Induced By Human Serum Albumin

Melatonin(MT) was a substance which had strong ability in neuroendocrine-immunoregulation and in free radical scavenging systems. It was well known that the immunologic hepatic fibrosis(IHF) expressed abnormal imrnunoregulation and radical attack, MT receptors had been found in rodent lymphocytes and hepatocytes. It has been reported that MT participates in regenerating liver and lymphoid morphostasis of hepatectomized rats, and also prevents oxidative liver injury, which suggested that MT might protect liver damage via immunoregulatory and directly antioxidative effects. In order to explore the effects of MT on IHF, a series of works have been done in our lab, the main results as follow: 1. The charaters of rats IHF induced by human serum albumin After the establishment of IHF rats model, we found that, in serum and liver homogenates, the levels of nitric oxide(NO), malondialdehyde(MDA) obvious increased and the activity of superoxide dismutase(SOD) and glutathione peroxidase(GSHpx) significant decreased, respectively. The pathologic changes of liver included the infiltration cells such as lymphocytes, mononuclear cells around portal area and centric veins, the injury of hepatocytes, the disorgnization of lobular. These evidences indicated that the hepatic cirrhosis formed already. Meanwhile, the collagenous fiber in portal area proliferatied remarkably, distributed along sinoid scattly, and surrounded lobular connectively. 2. Effects of MT on rats IHF induced by human serum albumin MT(0.3 mg kg?0.6 mg kg抯 0.9 mg kg? was given daily ig for 9 weeks at the beginning of attacking stages. The results showed that MT could attenuated the elevation of NO and MDA, reverse the decreased SOD and GSHpx levels in liver and serum respectively. Otherwise, MT(0.3 mg kg?~. 0.6 mg kg?~ 0.9 mg kg? could attenuate the degree of hepatic fibrosis and collagenous fibrous proliferation. The results suggest that MT has certain effects on the rats with IHF. The mechanisms may be related to its inununoregulatory actions and ability of scavenging free radical. This work may give us a new idea on prevention and treatment for human hepatic fibrosis.