实验性肝纤维化大鼠MMPs和TIMPs mRNA表达及中药小柴胡汤的作用

MMPs and TIMPs mRNA Expression and the Effect of Shosaikoto in Experimental Rat Liver Fibrosis

目的探讨大鼠肝纤维化过程中MMP-2、TIMP-1mRNA表达及小柴胡汤对其的影响。方法用40%的四氯化碳制备大鼠肝纤维化模型,并用不同剂量的小柴胡汤进行干预。应用HE常规染色法对肝组织切片行组织病理学检查;应用逆转录聚合酶链反应法(RT-PCR)半定量测定大鼠肝组织中MMP-2、TIMP-1mRNA的表达。结果(1)肝组织病理学检查结果显示:小柴胡汤治疗组与模型组相比,肝纤维化程度显著减轻。(2)病理模型组TIMP-1mRNA与正常对照组比明显升高(P<0.01);而MMP-2mRNA却明显降低(P<0.05)。(3)小柴胡汤治疗组TIMP-1mRNA与模型组比显著降低(P<0.01),而MMP-2mRNA与模型组无差异(P>0.05)。结论TIMP-1mRNA在肝纤维化过程中升高;小柴胡汤能显著减轻大鼠肝纤维化程度,其可能通过下调TIMP-1mRNA的表达发挥作用。

Objective To investigate MMP-2 and TIMP-1 mRNA and the effect of shosaikoto in hepatic fibrosis rats. Methods The hepatic fibrosis model was induced by intraperitoneal injection of 40% CCl4 and interfered with different dose of shosaikoto. Tissue sections were stained with routine HE. The mRNA of MMP-2 and TIMP-1 were measured by semi quantitation reverse transcriptase polymerase chain reaction（RT-PCR）. Results （ 1 ） In comparision with model group. The degree of proliferation of collagenous fibers in the liver reduced significantly in the theraputic groups. （ 2 ） The expression of TIMP-1 in model group increased significantly compared with normal control group（ P 〈0.01 ） ,While the expression of MMP-2 mRNA in the model group reduced significantly compared with normal control group（ P 〈 0. 05 ）. （3）TIMP-1 mRNA in the theraputic group reduced significantly compared with model group（ P 〈0. 01 ） ,while the difference in the MMP-2 mRNA was not statistically significant between theraputic and model groups（ P 〉0.05）. Conclusion Shocaikoto can significantly reduce the proliferation degree of collagenous fiber. It down-regulates the expression of TIMP-1 mRNA in liver fibrosis.