黄芪对肝纤维化大鼠肝组织TIMP-1及MMP-1表达的影响

Influences of Huangqi( Radix Astragali seu Hedysari) on expressions of TIMP-1 and MMP-1 in liver tissues in rats with liver fibrosis

目的观察黄芪对免疫肝纤维化模型大鼠血清肝纤维化标志物及肝组织金属蛋白酶抑制剂-1(TIMP-1)及基质金属蛋白酶(MMP-1)表达的影响。方法 40只Wistar大鼠随机分为正常组、模型组、黄芪治疗组、秋水仙碱组。除正常组外,其余各组均给予腹腔注射无菌猪血清,每周2次,连续12周;同时正常组、模型组每日灌服蒸馏水,其余各组灌服相应药物;采用生化、放射免疫、ELISA法观察免疫肝纤维化大鼠血清肝功能,肝纤维化标志物血清透明质酸(HA)、层黏连蛋白(LN)、Ⅳ型胶原(CⅣ)、Ⅲ型前胶原(PCⅢ),肝组织TIMP-1及MMP-1含量的变化。结果与模型组比较,黄芪治疗组可以使肝纤维化大鼠的血清HA、CⅣ显著降低(P<0.01),肝组织MMP-1显著升高,TIMP-1显著下降。结论黄芪可有效降低肝纤维化血清学指标,并可使肝组织纤维化程度有明显改善,其作用机理与其能够增加肝组织中MMP-1的表达,降低TIMP-1的表达,使得细胞外基质(ECM)降解增多,合成减少,从而抑制ECM的堆积,达到改善肝组织肝纤维化程度的目的。

Objective To observe the influences of Huangqi （Radix Astragali seu Hedysari） on serum liver fibrosis markers and expressions of tissue inhibitor of metalloproteinase-1 （TIMP-1） and matrix metalloproteinase-1 （ MMP-1 ） in liver tissues in rat model of immune liver fibrosis induced by pig serum. Methods Wistar rats （n = 40） were randomly divided into normal group, model group, Huangqi group and colchicinum group. Excepting normal group, other groups were injected intraperitoneally sterile pig blood twice a week for 12 weeks. Meanwhile, normal group and model group were intragastrically given distilled water every day, and of liver function, liver fibrosis IV （ C IV ） and pro-collagen other groups were intragastrically given corresponding drugs. The markers including serum hyaluronic acid （HA）, laminin （LN）, Ⅲ （PC Ⅲ ）, and TIMP-1 and MMP-1 levels were detected changes collagen by using biochemical assay, radioimmunoassay and ELISA. Results The levels of serum HA and C IV, and level of TIMP-1 decreased significantly, and the level of MMP-1 in increased significantly in Huangqi group compared with those in model group （P 〈 0. 01 ）. Conclusion Huangqi can effectively reduce the levels of serum indexes of liver fibrosis, and remarkably ameliorate the degree of liver fibrosis. The mechanism may be related to that it extracellular matrix （ECM） can increase MMP-1 expression, decrease TIMP-1 expression, improve degradation and decrease ECM synthesis, so as to suppress the accumulationof ECM and ameliorate the fibrosis degree of liver tissues.