硫酸软骨素对大鼠酒精性肝纤维化模型的影响

Study on the effect of chondroitin sulfate on fibrotic liver induced by alcohol in rats

探讨硫酸软骨素对酒精性肝纤维化的治疗作用。用连续灌服酒精的方法建立大鼠酒精性肝纤维化模型,在造模成功后给予硫酸软骨素治疗6周(25mg/Kg,腹腔注射,每天一次)。测定血清和肝脏匀浆一氧化氮(NO)和一氧化氮合酶(NOS)的表达,免疫组化检测肝组织血小板源性生长因子(PDGF)、金属蛋白酶组织抑止因子1(TIMP-1)、Ⅰ型胶原和Ⅲ型胶原的表达。硫酸软骨素能减轻酒精性肝纤维化的组织病理改变,降低酒精性肝纤维化大鼠肝组织胶原纤维和TIMP-1的表达。酒精性肝纤维化中,血清和肝脏匀浆NO和NOS的表达增加,肝脏组织PDGF的表达增加,使用硫酸软骨素可显著抑制NO、NOS和PDGF的表达(P<0.01)。硫酸软骨素对酒精性肝纤维化有治疗作用,其作用机制可能与影响NO、NOS和PDGF的表达水平相关。

The roles of chondroitin sulfate on fibrotic liver induced by alcohol in rats were investigated.The fibrotic liver model in rats was induced by alcohol for 24 weeks.Chondroitin sulfate was injected intra-abdominally to the rats,25 milligram per kilogram every day for 6 weeks.The levels of nitric oxide and nitric oxide synthase in serum and liver homogenate were detected.The level of collagen in liver tissue was detected by Van Gieson dye.The level of platelet derived growth factor(PDGF) and tissue inhibitor metalloproteinase-1(TIMP-1) in liver tissue were detected by immuno-histochemistry.The results showed that chondroitin sulfate could improve the pathological changes of liver tissue,and decreased the level of collage and TIMP-1.NO,NOS and PDGF expression levels were increased in fibrotic liver induced by alcohol.However,NO,NOS and PDGF expression were inhibited after administration of chondroitin sulfate.It was suggested that chondroitin sulfate might have therapeutic effects on fibrotic liver induced by alcohol in rats by decreasing the levels of NO,NOS and PDGF.