目的 探讨乌司他丁对大鼠肝纤维化过程的影响.方法 18只TAA诱导的肝纤维化模型大鼠分为3组:正常大鼠为A组(3只),模型鼠+生理盐水为B组(9只),模型鼠+乌司他丁为C组(9只)并干预3周.对比干预前后大鼠血清中的丙氨酸转氨酶(alanine aminotransferase,ALT)、天冬氨酸转氨酶(aspartate aminotransferase,AST)、超氧化物歧化酶(Superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、透明质酸(hyaluronic acid、HA)、层粘连蛋白(laminin,LN)水平变化.病理学检查及免疫组化观察各组大鼠肝形态学变化及转化生长因子β1(transforming growth factor β1,TGF-β1)、caspase-3蛋白表达.结果 C组干预后大鼠肝脏弹性数值及SSS评分与干预前相比显著降低,差异有统计学意义(t=2.472,P<0.05).C组的ALT、AST、SOD、MDA、HA、LN生化指标均有不同程度的好转(分别F=3.862、5.774、3.442、4.157、4.173、3.674,均P<0.05).HE及Masson染色可见干预后C组大鼠肝组织有少量炎性细胞浸润,肝细胞坏死灶并未增多,胶原纤维略有增生.C组TGF-β1、caspase-3阳性细胞率明显低于B组大鼠. 结论 乌司他丁对大鼠肝纤维化具有逆转作用,使大鼠肝脏纤维化程度逐渐减轻,减少胶原纤维的沉积,抑制肝细胞炎症.
Objective To explore if Ulinastai reverses hepatofibrosis in rats.Method Rat hepatofibrosis models were induced by TAA subcutaneously injection.18 rats with hepatofibrosis were divided into 2 groups,Ulinastai treatment group (9 rats),normal saline control group (9 rats).AST,ALT,HA,SOD,MDA,LN level were measured and compared between the 2 groups and that of healthy rats (3 rats).Rats liver morphology was observed using HE,Masson stain and type-B ultrasonic.TGF-β1、caspase-3 were detected by immunohistochemistry.Result After 3 weeks Ulinastai treatment,elastic index and SSS score in Ulinastai group decreased significantly compared to pretreatment (t =2.472,P <0.05).ALT,AST,SOD,MDA,HA and LN level significantly improved (F =3.862,5.774,3.442,4.157,4.173,3.674,P < 0.05).Compared with NS treatment group HE and Masson staining showed fewer inflammatory cells infiltration in central vein,ballooning degeneration of liver cells,collagen proliferated,hepatic lobules degradation and pseudolobule arise after 3 weeks intervenion.Also in Ulinastai group,TGF-β1、caspase-3 positive cells were much less than that in NS treatment group.Conclusions Ulinastai can reverse rat hepatic fibrosis and alleviate fibrosis degree and collagen fiber deposit.