Objective: To investigate the preventive and therapeutic effects of Qiwei Yugan Granule (QYG) on hepatic fibrosis in rats based on MMP-13/TIMP-1 imbalance. Methods: The rats were randomly divided into control group, model group, colchicine group (1.0×10-4 g/kg) and QYG treated groups (3.7, 7.4, 14.8 g/kg) (n=8). The rat model of hepatic fibrosis was established by injected with carbon tetrachloride subcutaneously for 4 weeks and treated with ethanol by gavage for 6 weeks. The effects of QYG on liver function, histopathology of liver, related indexes of serum liver fibrosis, and MMP-13, TIMP-1 in hepatic tissue were observed. Results: QYG at the doses of 14.8、7.4、3.7 g/kg could significantly decrease the serum levels of ALT, AST, HA, PCⅢ and C-Ⅳ, relieve the pathological changes of hepatic fibrosis, increase the activity of MMP-13, decrease the activity of TIMP-1 and alleviate the imbalance of MMP-13/TIMP-1. Among them, QYG had a certain trend of dose-effect relationship with TIMP-1 and MMP-13/TIMP-1 (P＜0.05, 0.01). Conclusion: QYG has the effect of preventing and treating liver fibrosis and one of mechanisms is to promote MMP-13/TIMP-1 to restore balance.
目的: 探讨七味育肝颗粒对肝纤维化大鼠的防治作用及对基质金属蛋白酶-13(MMP-13)/基质金属蛋白酶抑制因子-1(TIMP-1)失衡的影响。方法: 取大鼠随机分为空白对照组、模型对照组、秋水仙碱组(1.0×10-4 g/kg)、七味育肝颗粒各干预组(3.7、7.4、14.8 g/kg)组(n=8),采用皮下注射四氯化碳、灌胃乙醇6周来复制肝纤维化动物模型,造模的同时给药组每天灌胃给药,观测七味育肝颗粒对大鼠肝功能、肝组织病理学及肝纤维化相关指标的影响,采用免疫组化法测定肝组织MMP-13、TIMP-1的表达水平。结果: 与空白对照组比较,模型对照组大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)以及肝组织透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(C-Ⅳ)、TIMP-1显著升高,而MMP-13显著下降,缓解肝组织纤维化病理变化(P＜0.01);与模型对照组比较,3.7、7.4、14.8 g/kg七味育肝颗粒能明显降低ALT、AST以及HA、PCⅢ、C-Ⅳ,缓解肝组织纤维化病理变化,改善肝功能,提高MMP-13活性而降低TIMP-1活性,缓解MMP-13/TIMP-1的失衡状态(P＜0.05, P＜0.01),其中七味育肝颗粒对TIMP-1及MMP-13/TIMP-1的影响有一定的量效关系趋势(P＜0.01)。结论: 七味育肝颗粒具有防治肝纤维化的作用,而改善MMP-13/TIMP-1平衡状态可能是七味育肝颗粒防治肝纤维化作用的机制之一。.
Keywords: Qiwei Yugan Granule (QYG); hepatic fibrosis; matrix metalloproteinase - 13 (MMP-13) /tissue inhibitor of metalloproteinase - 1 (TIMP-1); rat; therapeutic effect.