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目的:观察干扰素-α(interferon-alpha,IFN-α)对猪血清诱导大鼠肝纤维化的治疗作用,并探讨其机制。方法:45只雄性Wistar大鼠,完全随机分为正常组、模型组和IFN-α治疗组,每组15只。正常组予0.9%氯化钠注射液,模型组和IFN-α组予猪血清,腹腔注射、每次0.5mL/只,2次/周,共12周;IFN-α组于第9周给予每天IFN-α10×104U/只,皮下注射,治疗4周。于12周末处死所有大鼠,取肝组织行HE染色进行炎症活动度半定量评分;免疫组织化学法检测Ⅰ型胶原、Ⅲ型胶原、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)的表达;Real-time PCR法检测金属蛋白酶组织抑制剂-1(tissue inhibitor ofmetalloproteinase-1,TIMP-1)mRNA表达。结果:模型组肝炎症活动度半定量评分高于正常组(P<0.001),IFN-α组较模型组降低37.56%(P<0.01);模型组I型、Ⅲ型胶原、α-SMA蛋白表达高于正常组(P<0.001),IFN-α组较模型组分别降低58.39%,52.63%,64.07%(P<0.001);模型组TIMP-1mRNA高于正常组(P<0.001),IFN-α组较模型组降低59.06%(P<0.01)。结论:IFN-α具有抗猪血清诱导的大鼠肝纤维化作用,其机制可能与减轻肝炎症程度,抑制肝星状细胞活化,降低大鼠肝组织Ⅰ型、Ⅲ型胶原的含量,阻止细胞外基质合成有关;另外,也与降低TIMP-1mRNA表达,减少TIMP-1对金属基质蛋白酶的抑制而促进细胞外基质的降解有关。
Objective: To observe the therapeutic effect of interferon-α (IFN-α) on rat liver fibrosis induced by porcine serum and its mechanism. Methods: Forty-five male Wistar rats were randomly divided into normal group, model group and IFN-α treatment group, 15 rats in each group. 0.9% sodium chloride injection was given to the normal group, and the porcine serum was injected into the model group and the IFN-α group by intraperitoneal injection at a dose of 0.5 mL / time for 2 weeks / week for 12 weeks. The IFN-α group was given at the 9th week IFN-α10 × 104U / day, subcutaneously, for 4 weeks. At the end of 12 weeks, all the rats were sacrificed, and the liver tissues were harvested for semi-quantitative scoring of inflammatory activity by HE staining. The expression of collagen type Ⅰ, type Ⅲ collagen and α-smooth muscle actin (α- SMA). Real-time PCR was used to detect the mRNA expression of tissue inhibitor of metalloproteinase-1 (TIMP-1). Results: The semi-quantitative score of liver inflammation activity in model group was higher than that in normal group (P <0.001), IFN-α group decreased by 37.56% (P <0.01), the expression of type I collagen, type Ⅲ collagen, (P <0.001). The levels of TIMP-1 mRNA in model group were significantly higher than those in normal group (P <0.001), IFN-α group was lower than that of model group by 58.39%, 52.63% and 64.07% -α group than the model group decreased 59.06% (P <0.01). CONCLUSION: IFN-α has the anti-pig serum-induced hepatic fibrosis in rats. The mechanism may be related to the reduction of hepatic inflammation, inhibition of hepatic stellate cell activation, reduction of type Ⅰ and type Ⅲ collagen in rat liver tissue, In addition, it is also related to the decrease of TIMP-1 mRNA expression, the decrease of TIMP-1 inhibition of metal matrix protease and the promotion of the degradation of extracellular matrix.