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目的明确虫草菌丝提取物(Cordyceps mycelia extract,CME)对二甲基亚硝胺(dimethylnitro-samine,DMN)诱导大鼠肝硬化的干预与治疗作用。方法采用DMN10μg/kg剂量腹腔内注射,每日1次,每周前3日、持续4周的方法制备大鼠肝硬化模型。CME干预实验于造模即日起开始灌胃给药至造模4周末;治疗实验于造模4周、终止造模因素后开始给药至8周末;均以0.74g/(kg.d)剂量给予CME,每日1次。分别于造模后3天、2、4、6、8周处死动物取材进行动态效应观察。观测肝组织学、肝组织α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(ColⅠ)的免疫组织化学染色、肝羟脯氨酸(Hyp)含量以及肝功能的检测。结果与同期模型组比较,CME预防给药后2、4周的血清丙氨酸氨基转移酶(ALT)、血清门冬氨酸氨基转移酶(AST)活性和血清总胆红素(TBIL)含量均显著降低(P<0.05),血清白蛋白(Alb)含量显著增加(P<0.05);干预用药4周后的肝Hyp含量显著下降(P<0.05),胶原纤维增生程度显著减轻(P<0.05),肝组织内α-SMA、ColⅠ阳性表达显著减少(P<0.05)。与同期模型组比较,治疗给药2周后的血清ALT、AST活性和血清TBIL含量显著降低(P<0.05),血清Alb含量有所升高(P>0.05);治疗给药2、4周的肝Hyp含量均显著降低(P<0.05),胶原纤维增生程度均显著减轻(P<0.05),肝组织α-SMA表达均显著减少(P<0.05);治疗给药4周时肝组织ColⅠ表达显著减少(P<0.05)。结论CME既能显著抑制DMN大鼠肝硬化的形成,也可有效促进已成型的DMN大鼠肝硬化的逆转,具有良好的临床应用前景。
Objective To investigate the effects of cordyceps mycelia extract (CME) on dimethylnitrosamine (DMN)-induced liver cirrhosis in rats. Methods The rat liver cirrhosis model was prepared by intraperitoneal injection of DMN 10μg/kg, once daily, 3 days before the first week and 4 weeks after the treatment. The CME intervention experiment began to be intragastrically administered until the end of the model 4 weeks after the model was established. The treatment experiment was started 4 weeks after the model was established and the modeling factors were terminated. The dose was 0.74 g/(kg.d). Give CME once daily. Animals were sacrificed 3 days, 2, 4, 6 and 8 weeks after modeling to observe the dynamic effects. Observed liver histology, liver tissue α smooth muscle actin (α-SMA), type I collagen (ColI) immunohistochemistry, liver hydroxyproline (Hyp) content and liver function tests. Results Compared with the same model group, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) activity, and serum total bilirubin (TBIL) levels were prevented by CME at 2 and 4 weeks after administration. Both significantly decreased (P<0.05), serum albumin (Alb) content increased significantly (P<0.05); after 4 weeks of interventional therapy, liver Hyp content decreased significantly (P<0.05), collagen fiber proliferation significantly reduced (P< 0.05), the positive expression of α-SMA, ColI in liver tissue was significantly reduced (P<0.05). Compared with the same period model group, serum ALT, AST activity and serum TBIL content were significantly reduced (P<0.05) and serum Alb content was increased (P>0.05) after 2 weeks of treatment; The liver Hyp content was significantly decreased (P<0.05), collagen fiber proliferation was significantly reduced (P<0.05), and the expression of α-SMA in the liver tissue was significantly reduced (P<0.05); liver tissue ColI at 4 weeks after treatment Expression was significantly reduced (P<0.05). Conclusion CME can not only significantly inhibit the formation of liver cirrhosis in DMN rats, but also effectively promote the reversal of liver cirrhosis in DMN rats. It has a good clinical application prospect.