实验性肝纤维化模型肝组织MMP-2基因表达与酶活性及中药复方“861”的作用

The effect of herbal compound 861 on mRNA levels of MMP-2 and its activities in experimental rats liver fibrosis

目的 探讨肝纤维化发生后MMP 2的基因表达与酶活性的变化及复方“86 1”的影响。方法 4 5只雌性Wistar大鼠随机分为假手术组、胆管阻塞性肝纤维化模型组和复方“86 1”治疗组。术后第 7天开始治疗 ,4 9d后 ,采用半定量RT PCR法检测肝组织中MMP 2mRNA ,应用酶谱法检测肝组织中MMP 2酶活性。结果 模型组肝组织中MMP 2mRNA的表达比正常组高 ,差异有非常显著性(P <0 .0 0 1) ;而中药复方“86 1”治疗组肝组织中MMP 2mRNA的表达 ,与正常组比较差异无显著性 ,比模型组低 ,差异有非常显著性 (P <0 .0 0 2 )。正常组肝组织中未测到MMP 2酶活性 ;模型组肝组织中显示出一定MMP 2酶活性 ;而中药复方“86 1”治疗组肝组织中MMP 2酶活性比模型组显著升高 (P <0 .0 1)。结论 中药复方“86 1”能抑制MMP 2的基因表达 ,但又因可能解除MMP 2的抑制因素而提高其活性 ,以降解沉积的纤维性胶原而参与肝纤维化的逆转过程。

Objective To explore the effect of herbal compound 861 (Cpd 861) on MMP 2 expression and its enzymatic activities, and the antifibrotic mechanism of this herbal compound. Methods Forty five female rats were randomizedly divided into normal control (sham operation) group, common bile duct ligation (BDL) group and Cpd 861 therapeutic group. In the last group, daily gastric feeding of Cpd 861 (9 g/kg.bw) started on day 7 after BDL operation. At 49 days, all animals were sacrificed and mRNA expression of MMP 2 in liver tissue was evaluated by semi quantitive RT PCR. In addition, enzymatic activities of MMP 2 were analyzed by zymography. Results In comparison with model group, MMP 2 mRNA levels in Cpd 861 therapeutic group were significantly decreased. MMP 2 enzymatic activities were not detectable in normal group, slightly elevated in model group, higher in Cpd 861 therapeutic group. Conclusion Cpd 861 decreases the mRNA level of MMP 2, but transiently increases the enzymatic activities of MMP 2. The latter effect of Cpd 861 may be mediated by decreasing TIMPs, the inhibitors of MMPs, during resolution stage of fibrosis. This is probably one of the mechanisms whereby herbal Cpd 861 exerted its antifibrotic action in this kind of experimental liver fibrosis.