The Expression Of MMP-9 In Hepatic Sinusoidal Obstruction Syndrome Induced By Gymura Segetum

Background:Hepatic sinusoidal obstruction syndrome(HSOS) is a clinical syndrome characterized by painful hepatomegaly,ascites,increased body weight and jaundice. Gymura segetum,which is widely used in the Chinese traditional medicine,is identified to be related to the onset of SOS.Scientists consider the pyrrolizidine alkaloids(PAs) in the plant of Gymura segetum cause the SOS,though the pathogenesis is still unclear. Many experimental models were established to study its mechanisms or therapy,but few are ideal.This work aimed at a reproductible rat model of SOS and the possible role of matrix metalloproteinase 9 in the onset of the disease.Materials and Method:The alkaloids in gymura segetum were abstracted and analyzed at first.25 male Sprague-Dawley rats(200-250 g ) were divided into two groups randomly.20 of them were gavaged with 600mg/(Kg.d)Gymura segetum extract solution for three weeks.5 controls were gavaged with tap water alone.Liver sections were evaluated by light microscopy with a modified scoring system based on Deleve's.Routine transmission electron(TEM) methods for liver were used to evaluate the ultrastructual features of fixed livers of 25 rats.Blood samples were collected to determine liver enzyme concentrations.The positivity of matrix metalloproteinase-9(MMP-9)was estimated by both immunohistochemical staining and ELISA methods.All the data was analyzed by the statistical software package SPSS 16.0.Results:The rats gavaged with gymura segetum solution presented clinical symptoms and the histopathological manifestation of HSOS.Laboratory tests showed abnormal liver enzyme concentrations.Compared with controls,the activities of MMP-9 in HSOS rats increased prominently.Conclusions:Stable and reproducible rat model of HSOS can be set up by gavaging with gymura segetum in a long period.MMP-9 may play an important role in incomplete sinusoidal lining in early pathological changes of HSOS and thus induce the onset of the disease. The prominently high expression of MMP-9 in pulmonary tissues indicate its possible responsibility for the origin of pulmonary hypertension.