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    基于RhoA/ROCK通路探讨软肝冲剂对CCl4致大鼠肝纤维化的作用机制

    Exploring the Mechanism of Ruangan Granule on CCl4-induced Hepatic Fibrosis in Rats Based on RhoA/ROCK Pathway

      摘要
    • 摘要:
      目的 基于RhoA/ROCK通路探究软肝冲剂对CCl4致大鼠肝纤维化的保护作用及其分子机制。
      方法 大鼠灌胃给予2 mL·kg−1 40% CCl4(CCl4∶橄榄油=2∶3)每周2次，共8周，建立大鼠肝纤维化模型。造模第6周给予软肝冲剂干预8周，采用Masson染色、脏器指数、生化指标评价软肝冲剂对CCl4致大鼠肝纤维化的作用；采用RT-PCR、Western blotting及免疫荧光组织化学法检测大鼠肝脏组织中Coll Ⅰ、α-SMA、RhoA、ROCK 1 mRNA和蛋白质的表达。
      结果 脏器指数和生化指标结果显示，与模型组比较，软肝冲剂中剂量组能降低大鼠的肝指数(P<0.01)；软肝冲剂高、中剂量组能降低大鼠的脾指数(P<0.01或P<0.05)；软肝冲剂高、中、低剂量组均能提高大鼠的胸腺指数(P<0.05或P<0.01)；软肝冲剂可以不同程度降低大鼠的血清中AFP、ALT、AST水平(P<0.05或P<0.01)。Masson染色结果显示，软肝冲剂可以显著降低大鼠肝脏胶原纤维增生。RT-PCR、免疫荧光组织化学结果显示，软肝冲剂可以显著降低大鼠肝脏组织中Coll Ⅰ、α-SMA、RhoA、ROCK 1 mRNA和蛋白质的表达。Western blotting结果显示，与模型组比较，软肝冲剂各剂量组均能降低Coll Ⅰ、α-SMA、ROCK 1 蛋白质的表达，软肝冲剂中、低剂量组均降低RhoA 蛋白质的表达。
      结论 软肝冲剂对CCl4致大鼠肝纤维化的治疗作用可能与抑制RhoA/ROCK通路有关。

       

      Abstract:
      OBJECTIVE To explore the mechanism of Ruangan Granule against CCl4-induced hepatic fibrosis in rats based on RhoA/ROCK pathway.
      METHODS The rat hepatic fibrosis model was established by intragastric administration of 40% CCl4 (2 mL·kg−1)(CCl4∶olive oil=2∶3), twice a week for 8 weeks. After the intervention of Ruangan Granule at 6 week for 8 weeks, Masson staining, organ index and biochemical indexes were used to evaluate the effect of Ruangan Granule on CCl4-induced hepatic fibrosis in rats. RT-PCR, Western blotting and immunofluorescent tissue chemistry was used to detected the expression of Coll Ⅰ, α-SMA, RhoA, ROCK 1 mRNA and protein in rats.
      RESULTS The organ index and biochemical analysis indicated that, compared with the model group, the liver index of rats was decreased in the middle dose group(P<0.01), and the spleen index was decreased in the high and middle dose groups(P<0.05 or P<0.01); high, middle and low dose of Ruangan Granule could increase the thymus index of rats(P<0.05 or P<0.01); Ruangan Granule could reduce the levels of AFP, ALT and AST in the serum(P<0.05 or P<0.01). The results of Masson staining showed that Ruangan Granule could significantly reduce the proliferation of collagen fibers in rat liver. RT-PCR, immune fluorescent tissue chemistry results showed that Ruangan Granule could significantly downregulate the expression of Coll Ⅰ, α-SMA, RhoA, and ROCK 1 mRNA and protein. Western blotting results showed the protein expression of Colli, α-SMA and Rock-1 were decreased in all groups. The protein expression of RhoA was decreased in middle and low dose groups of Ruangan Granule.
      CONCLUSION The therapeutic effect of Ruangan Granule on CCl4-induced hepatic fibrosis in rats may be related to the inhibition of RhoA/ROCK pathway.

       

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