肝豆汤Ⅱ号干预治疗Wilson病患者肝纤维化机制探讨

The study on the mechanism of anti-fibrosis with Gan Dou Tang Ⅱ in the treatment of patients with Wilson's disease

目的观察我院经验方-肝豆汤Ⅱ号治疗对Wilson病(WD)患者血清基质金属蛋白酶-1(MMP-1)、金属蛋白酶-1组织抑制因子(TIMP-1)和其它肝纤维化血清学指标(HA、LN、PCⅢ、C-IV)以及肝功能的影响,进一步阐释该方抗肝纤维化作用机制。方法61例WD患者分为DMPS组(30例)和DMPS+肝豆汤Ⅱ号组(31例)。DMPS组单纯予DMPS驱铜治疗8个疗程,DMPS+肝豆汤Ⅱ号组予DMPS驱铜同时,口服肝豆汤Ⅱ号治疗8周。两组治疗前后分别采用双抗体夹心ABC-EIASA法检测血清MMP-1、TIMP-1;放射免疫法(RIA)检测血清HA、LN、PCⅢ、C-IV;全自动生化分析仪测定ALT等肝功能指标。结果DMPS组治疗前后所有肝纤维化血清学指标及肝功能指标变化不明显(P>0.05);而DMPS+肝豆汤Ⅱ号组治疗后血清TIMP-1水平明显下降(P<0.05),血清MMP-1/TIMP-1的比值明显升高(P<0.01);ALT等肝功能指标明显下降(P<0.05)而血清HA、LN、PCⅢ水平仅略有下降(P>0.05),血清C-IV、MMP-1亦仅略有升高(P>0.05)。结论WD患者短期内单纯驱铜治疗并不能改变血清MMP-1、TIMP-1等肝纤维化指标水平及肝功能,而联合应用肝豆汤Ⅱ号治疗可以改善肝功能,并且通过抑制TIMP-1的表达,提高MMP-1/TIMP-1的比值,即间接通过提高MMP-1对细胞外基质(ECM)的降解活性,而发挥抗肝纤维化作用。

Objective To observe the influence of Gan Dou Tang Ⅱ （ GDT - Ⅱ ） on serum MMP - 1 （ matrix metalloproteinase - 1 ）、TIMP - 1 （ tissue inhibitors of metalloproteinase - 1 ）、other fibrosis indexes such as HA、LN、PCⅢ,C - Ⅳ and indexes of liver function of patients with Wilson＇s disease and to exlplore the mechanism of anti - fibrosis with GDT - Ⅱ treatment Methods 61 WD patients were divided into two groups：30 patients in DMPS group and 31 patients in DMPS ＋ GDT - Ⅱ group. They received 8 courses of DMPS and DMPS ＋ GDT - Ⅱ treatment respectively. Before and after treatment, We checked serum MMP - 1、TIMP - 1 by ELISA、serum HA,LN ,PCⅢ、C -Ⅳ by radioimmunoassay （RIA） and serum TBIL、ALT、AST、G by biochemical analysis with automatic machine. Results In DMPS group, all indexes of liver fibrosis and liver function had no significant decrease or increase after 8 courses of DMPS treatment, while the level of serum TIMP - 1 had been markedly decreased （ P 〈0.05 ） and the ratio of MMP - 1/TIMP - 1 had been significantly increased （ P 〈 0.01 ） after treatment in DMPS ＋ GDT - Ⅱ group, and the level of serum TBIL、ALT、AST、G had also been markedly decreased （ P 〈 0.05 ） , but the level of serum HA、LN、PCⅢ had been slightly decreased（ P 〉 0.05 ） and serum MMP - 1 ,C - Ⅳ had been slighted increased（ P 〉 0.05 ） Conclusion A shout -termed decoppering treatment with DMPS have no significient influence on serum MMP - 1 ,TIMP - 1 and indexes of liver function of patients with WD, but Treating combined with GDT - Ⅱ can improve liver function and significantly decrease the serum TIMP - 1 level and increase the ratio of MMP - 1/TIMP - 1 which could strengthen collagen decomposition and have an anti - fibrosis role in the treatment of WD.