论文部分内容阅读
目的:探讨消癖丸干预二甲基亚硝胺(dimethylnitrosamine,DMN)诱导的大鼠肝纤维化的作用。方法:采用0.5%的DMN溶液2mL/kg体质量腹腔注射,每周连续注射3d,每日1次,共4周,制备大鼠肝纤维化模型。第3周开始模型大鼠随机分为模型对照组和消癖丸组,消癖丸组给予消癖丸煎剂灌胃,模型对照组给予等量的生理盐水。治疗2周后,观察大鼠肝功能、肝组织病理学改变及肝纤维化相关指标α平滑肌肌动蛋白(alpha-smooth muscle actin,α-SMA)、转化生长因子β1(transforming growth factor-β1,TGF-β1)、组织金属蛋白酶抑制剂1(tissue inhibitor of metalloproteinase-1,TIMP-1)和血红素氧合酶1(heme oxygenase-1,HO-1)表达的变化。结果:(1)与正常大鼠比较,造模2和4周时模型大鼠血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、碱性磷酸酶(alkaline phosphatase,ALP)活性逐渐升高(P<0.01或P<0.05),4周时血清总胆红素(total bilirubin,TBil)含量显著增加(P<0.05);与4周模型组比较,消癖丸组血清ALT、AST、ALP、TBil水平均显著降低(P<0.01或P<0.05)。(2)模型大鼠肝组织炎症反应及胶原沉积逐渐加重,4周时部分大鼠肝组织已形成完整包绕的假小叶结构,肝组织羟脯氨酸(hydroxyproline,Hyp)含量显著增加(P<0.01);与4周模型组比较,消癖丸组肝组织炎症、胶原沉积明显减轻,肝组织Hyp含量显著降低(P<0.05)。(3)模型大鼠肝组织α-SMA蛋白表达逐渐增加,4周时显著高于2周模型组(P<0.01);聚合酶链式反应分析显示,肝组织α-SMA、TGF-β1、TIMP-1和HO-1mRNA的表达随着模型的进展逐渐升高(P<0.01);与4周模型组比较,消癖丸组肝组织α-SMA蛋白的表达及α-SMA、TGF-β1、TIMP-1、HO-1mRNA的表达均显著降低(P<0.01或P<0.05)。结论:消癖丸能够显著抑制DMN诱导大鼠肝纤维化的进展,且这一作用机制可能与抑制肝星状细胞活化有关。
Objective: To investigate the effect of Xiaoji pill on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Methods: The rat model of hepatic fibrosis was established by intraperitoneal injection of 0.5% DMN solution 2 mL / kg body weight and continuous injection of three days a week for 4 weeks. At the beginning of the third week, the model rats were randomly divided into the model control group and the Xiaojiwan group. The Xiaojiwan group was given Fukaiwan decoction orally and the model control group was given the same amount of normal saline. After 2 weeks of treatment, the liver function, the pathological changes of liver tissues and the expressions of α-SMA, α-SMA and transforming growth factor-β1 (TGF-β1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and heme oxygenase-1 (HO-1) Results: (1) Compared with normal rats, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), aspartate aminotransferase (AST) The activity of alkaline phosphatase (ALP) increased gradually (P <0.01 or P <0.05) and the content of total bilirubin (TBil) increased significantly at 4 weeks (P <0.05) The levels of serum ALT, AST, ALP and TBil in Xiaoji pill group were significantly decreased (P <0.01 or P <0.05). (2) Inflammatory reaction and collagen deposition gradually increased in the liver of model rats. At 4 weeks, some rat liver tissues formed a complete surrounding pseudolobule structure, and the content of hydroxyproline (Hyp) in liver tissue increased significantly (P <0.01). Compared with the 4-week model group, the hepatic inflammation and collagen deposition in the Xiaojin pill group was significantly reduced and the Hyp content in the liver tissue was significantly decreased (P <0.05). (3) The expression of α-SMA protein in hepatic tissue of model rats increased gradually, which was significantly higher at 4 weeks than that of 2-week model group (P <0.01). The results of polymerase chain reaction showed that α-SMA, The expression of TIMP-1 and HO-1mRNA gradually increased with the progression of the model (P <0.01). Compared with the 4-week model group, the expression of α-SMA and the expressions of α-SMA and TGF- , TIMP-1, HO-1mRNA expression were significantly lower (P <0.01 or P <0.05). Conclusion: Xiaoji pill can significantly inhibit the progression of DMN-induced hepatic fibrosis in rats, and this mechanism may be related to the inhibition of hepatic stellate cell activation.