猪血清肝纤维化大鼠肝组织基质金属蛋白酶-9/13和基质金属蛋白酶组织抑制因子-1/2表达的动态变化及下瘀血汤对其影响

目的:研究免疫性肝纤维化大鼠肝组织基质金属蛋白酶9/13和基质金属蛋白酶组织抑制因子1/2表达的动态变化及下瘀血汤对其影响,探讨下瘀血汤抗肝纤维化的机制。方法:猪血清腹腔复制大鼠肝纤维化模型,造模8周后ig下瘀血汤的流浸膏,用药4周后和在造模过程中的1、24、、8周动态处死大鼠,获取标本,检测指标。结果:MMP-2/9的高活性和TIMP-1的高表达贯穿于本模型的始终。MMP-9/13蛋白表达在肝纤维化发生发展过程中有先抑制后升高,再次抑制而后升高的反复过程,并受TIMP-1/2表达影响;下瘀血汤可以提高MMP-9活性,促进MMP-9/13而抑制TIMP-1,2表达。结论:该模型有MMP-9/13和TIMP-1/2表达的失衡;下瘀血汤可通过调控MMp-9/13和TIMP-1/2的表达,降解过度沉积的细胞外基质而发挥抗肝纤维化的作用。

Expression of Matrix Metalloproteinase 9/13(MMP-9/13)and Tissue Inhibitor of Metalloproteinase 1/2(TIMP-1/2)in Liver Fibrosis Induced by Porcine Serum and Xiayuxue Decoction on It

Objective:Changes of protein expression of MMP-9/13 and TIMP1/2 in fibrotic liver tissue induced by porcine serum and effect of Xiayuxue Decoction on it are investigated in this study to explore mechanism of Xiayuxue Decotion in reversing it.Methods:Liver fibrosis in rats was induced by intraperitoneal injection of porcine serum.After 8wk of modeling,rats were given Xiayuxue Decoction for 4 weeks.Rats were sacrificed and sample was obtained for determination at 1 wk,2 wk,4 wk,8 wk and the end of 12 wk of modeling for determination.Results:High activity of MMP-2/9 and high expression TIMP-1 characterizes this liver fibrosis model from beginning to the end.Decreased protein expression of MMP-9/13 in early stage and increased protein expression of MMP-9/13 in early stage and increased protein expression of MMP-9/13 affect by protein expression TIMP-1/2.Xiayuxue Decoction can increase activity of MMP-9,promote expression of MMP-9/13,inhibit expression of TIMP-1/2.Conclusions:Imbalanced MMP-9/13 and TIMP-1/2 expression is seen in this model.The anti-liver fibrosis mechanism of Xiayuxue Decoction is regulating MMP-9/13 and TIMP-1/2 expression to degrade excessive deposition of extracellular matrix.