Effects Of Prednisone On IL-6, IL-8 And HSP-70 Expression In A Mice Model Of Hepatic Veno-occlusive Disease Induced By Gynura Segetum

Background:Hepatic veno-occlusive disease/hepatic venular occlusive disease (VOD/HVOD) is histologically characterized by non-thrombotic occlusion of liver venule and mainly manifested as hepatomegaly, right upper quadrant pain, jaundice and ascites. Gynura segetum has the effects of eliminating stasis to activate blood circulation and arresting bleeding, and is often used to treat bruises, wounds bleeding, haematemesis and puerperal abdominalgia with blood stasis. Gynura segetum was reported to have liver toxicity, and Gynura segetum-induced HYOD may be associated with pyrrolidine alkaloids (pyrrolizidine), but the pathogenic mechanism is not fully identified. It was reported that many cytokines participated in the development of liver fibrosis, such as IL-6, IL-8 and HSP, whether these cytokines are also involved in the occurrence and development of HVOD is not clear. Prednisone is an adrenal cortex hormone and adrenocorticotropic hormone drug, with anti-inflammatory, anti-allergic, anti-rheumatic and immune inhibition effects. Prednisone can inhibit the expression of several cytokines, such as IL-6, IL-8 and HSP-70, whether prednisone could prevent the progression of HVOD by inhibiting the expression of these cytokines has not been investigated.Methods:115 mice were randomly divided into 4 groups:blank control group (intragastric administration of 30ml/kg/d PBS buffer in a volume of 0.6ml for 30 days, n= 25), Gynura segetum group (100g Gynura segetum physic liquor equivalent to lg/mL crude drug, intragastric administration of 30 ml/kg/d in a volume of 0.6ml for 30 days, n= 30), prednisone intervention group 1 (intragastric administration of 5mg/kg/d prednisone in a volume of 0.2ml with Gynura segetum for 30 days, n= 30), prednisone intervention group 2 (intragastric administration of 10 mg/kg/d prednisone in a volume of 0.2ml with Gynura segetum for 30 days, n= 30). HVOD mice model was established by intragastric administration of Gynura segetum. IL-6, IL-8, HSP-70 expression in liver tissue specimens from experimental animals were detected by immunohistochemistry. Data was analyzed by SPSS 13.0 software package.Results:The mice which received Gynura segetum had similar clinical symptoms with HVOD; light microscopy confirmed that pathological features of liver specimens were also in line with HVOD. Immunohistochemistry found that liver IL-6 and HSP-70 level in Gynura segetum group were significantly higher than control group (30.99±14.49 vs 93.42±9.25 29.62±1.91 vs 140.00±12.68, P<0.05). In prednisone intervention group 1 and group 2, IL-6 and HSP-70 expression was not elevated. IL-8 level had no significant difference among these four groups (P>0.05).Conclusion:HVOD mice model was successfully established by intragastric administration of Gynura segetum. IL-6 and HSP-70 levels were significantly increased in HVOD animal liver tissue, indicating the elevation of IL-6 and HSP-70 may be related to the pathogenesis of HVOD; prednisone treatment reduced animal liver tissue IL-6 and HSP-70 levels, indicating that prednisone might play a role in blocking the pathogenesis of HVOD; blocking HVOD could be achieved with low dose of prednisone, and the specific mechanisms needs to be further explored.