抗纤复方药物血清对HSC-LI90细胞Ⅰ型、Ⅳ型前胶原和基质金属蛋白酶及其组织抑制因子-1基因表达的影响

目的：探讨抗纤复方药物血清对肝星形细胞(HSC)L190细胞(HSC—L190)I型、Ⅳ型前胶原和基质金属蛋白酶(MMPs)及其组织抑制因子(TIMP—1)基因表达的影响。方法：以0．5、2．0、4．0g／kg等不同剂量抗纤复方灌胃大鼠，制备药物血清，作用于HSC—L190细胞48h，应用Northern印迹杂交的方法，检测I型、Ⅳ型前胶原、基质金属蛋白酶-2(MMP-2)及膜型基质金属蛋白酶(MT1-MMP)及其组织抑制因子(TIMP-1)基因的表达，并用酶图法检测基质金属蛋白酶-2的活性：结果：(1)抗纤复方不同浓度药物血清能抑制HSC—L190细胞I型、Ⅳ型前胶原及其组织抑制因子TIMP-1的基因表达(P<0．05或P<0．01)；(2)能增加膜型基质金属蛋白酶基因表达(P<0．01)；(3)对基质金属蛋白酶-2基因表达及活性无影响(P>0．05)。结论：(1)抗纤复方具有抗肝纤维化作用；(2)抗纤复方抑制HSC-LI90细胞TIMP-1基因表达水平，促进胶原降解，可能是抗肝纤维化的作用机制之一。

Effect of anti-fibrosis compound contained serum on procollagen Type I and IV, matrix metalloproteinase and its tissue inhibitor-1 gene expression in HSC-LI90 cell line]

OBJECTIVE: To study the effects of Anti-fibrosis Compound contained serum (AFCS) on procollagen type I and IV (ProC-I and ProC-IV), matrix metalloproteinase (MMP) and its tissue inhibitor (TIMP-1) gene expression in hepatic stellate cell line LI90 (HSC-LI90). METHODS: AFCS was prepared by gastric infusing different dosage (0.5 g/kg, 2.0 g/kg and 4.0 g/kg) of Anti-fibrosis Compound Recipe to rats. After HSC-LI90 cells were exposed to AFCS for 48 hrs, levels of ProC-I, ProC-IV, gene expression of MMP-2, MMP membrane type 1 (MT1-MMP) and TIMP-1 in the cells were detected by Northern blot, and gelatinase activity of MMP-2 was measured by zymography. RESULTS: AFCS of different concentrations could inhibit ProC-I and ProC-IV and TIMP-1 gene expression (P < 0.05 or P < 0.01), increase MT1-MMP gene expression (P < 0.01), but it showed no effect on gene expression and activity of MMP-2 (P > 0.05). CONCLUSION: Anti-fibrosis Compound Recipe has anti-liver fibrosis action, its effects in inhibiting TIMP-1 gene expression of HSC-LI90 cells and promoting degradation of collagen might be one of the mechanisms of the action.