【摘要】 目的　通过观察酒精性肝纤维化形成过程中肝组织内骨调素 (Osteopontin、OPN)变化规律 ,初步探讨骨调素在酒精性肝纤维化形成过程中的作用及其机制。方法　用白酒 玉米油 吡唑混合液灌胃制造酒精性肝纤维化大鼠模型 ,选用纯系Sprague Dawley雄性大鼠 66只 ,体重在 180g～ 2 0 0g之间 ,将大鼠随机分成 6组 (每组 11只 ) ,A组为正常对照组 ,予以正常饮食。B组、C组、D组、E组、F组大鼠每天清晨用白酒 玉米油 吡唑混合液灌胃 ,分别于灌胃 2周、4周、8周、12周、16周后行股静脉采血 ,处死大鼠 ,并留取肝组织标本 ,分别测定肝功能 (ALT、AST)、血清肝纤维化指标 (HA、LN、CⅣ ) ;并作肝组织常规HE、Masson胶原染色及通过免疫组化染色、原位杂交技术动态观察肝组织中骨调素、α 肌动蛋白 (d SMA)表达、分布状况、定量和相关分析。结果　与对照组比较 ,酒精灌胃 4周、8周、12周、16周组大鼠OPN、α SMA表达显著增强并且肝内胶原纤维含量显著增加。正常肝组织中几乎不表达OPN ,在酒精性肝纤维化大鼠模型的建立过程中 ,从第四周开始中央静脉和邻近肝窦内皮细胞OPN的表达显著上调 ,并与胶原纤维面积百分比呈明显正相关 (r =0 .88)。结论　在酒精性肝纤维化大鼠模型中 ,OPN在肝组织中显著表达 ,并可能在酒精性?更多还原

【Abstract】 Ojective To investigate the role of osteopontin(OPN) in the alcoholic hepatic fibrosis through changes of OPN and α-SMA expression in the liver of rat model of alcoholic hepatic fibrosis.Methods Rat alcoholic hepatic fibrosis was induced by alcoholic,maize oil and pyrazole.Sixty six male Sprague-Dawley rats were randomly divided into control group,and 5 model hepatic fibrosis groups perfused alcoholic,maize oil and pyrazole for 2 weeks,4 weeks,8 weeks, 12 weeks and 16 weeks (11 rats in each group) respectively.Excepting rats in control group,all rats via gastrogavage were perfused of 56% alcoholic(from 8g/kg/d to12 g/kg/d),maize oil (2g/kg/d) and pyrazole(24mg/kg/d).Blood and liver tissue specimens were obtained after rats were sacrificed.Masson-Trichrome and immunohistochemical staining for Osteopontin (OPN) and α-SMA were performed. In situ hybridization of paraformaldehyde-fixed liver sections with OPN mRNA were performed.Results The morphometric measurement of the hepatic fibrosis in 4 weeks,8weeks,12 weeks,16 weeks groups were also markedly higher than those in control group (P<0.01).Immunohistochemical staining showed that expression of OPN, α-SMA in 4 weeks,8 weeks, 12 weeks, 16 weeks groups was increased dramatically compared with control group (P<0.01) . In situ hybridization histochemistry staining showed that expression of OPN mRNA in 4 weeks,8 weeks, 12 weeks, 16 weeks groups were also higher than those in control group (P<0.01) .OPN expression were closely correlated with macrophage infiltration and alcoholic hepatic fibrosis. Conclusion Expression of OPN was increased dramatically in the liver ,and may play an important role in rat model of alcoholic hepatic fibrosis.更多还原