芪参二莲汤对肝纤维化大鼠血清基质金属蛋白酶-1及其抑制剂-1水平的影响

Effects of Qishen Erlian Decoction on Serum MMP-1 and TIMP-1 in Liver Fibrosis Model Rats

目的观察芪参二莲汤对硫代乙酰胺(TAA)诱导大鼠肝纤维化的逆转作用和血清基质金属蛋白酶-1(MMP-1)及其抑制剂-1(TIMP-1)水平的影响,探讨其作用机制。方法采用TAA灌胃法制造肝纤维化模型,120只SPF级SD雄性大鼠按体质量随机分为正常组、模型组、秋水仙碱组和芪参二莲汤低、中、高剂量组,各给药组给予相应药物灌胃,正常组和模型组给予等量生理盐水灌胃,每日1次,连续5周。采用HE和Masson染色观察肝脏组织病理形态及损伤程度,采用生化分析、放免法、ELISA检测血清肝功能、肝纤维化四项及MMP-1、TIMP-1水平。结果与模型组比较,芪参二莲汤各剂量组均能显著降低大鼠血清丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、总胆红素、γ-谷氨酰转酞酶及透明质酸、层黏连蛋白、Ⅲ型前胶原、Ⅳ型胶原水平,MMP-1和MMP-1/TIMP-1比值显著升高,TIMP-1水平显著降低,差异均有统计学意义(P<0.05,P<0.01),并且存在一定的量效关系,以芪参二莲汤高剂量组疗效最佳。结论芪参二莲汤可明显改善肝纤维化大鼠肝功能及肝纤维化指标,调控MMP-1与TIMP-1水平,阻止肝纤维化病情的进展。

Objective To investigate the effects of Qishen Erlian Decoction on serum MMP-1and TIMP-1levels in thioacetamide(TAA)induced liver fibrosis rats;To discuss its mechanism of action.Methods Liver fibrosis model was created by the TAA gavage method.120SD male rats were randomly assigned to control group,model group,colchicine group,Qishen Erlian Decoction low-,medium-and high-dose group(20in each group).Each medication group was given relevant medicine for gavage.Control group and model group were given the same amount of normal saline for gavage,once a day for5weeks.HE staining and Masson trichrome staining were used to observe the pathological changes in liver tissue and liver tissue damage.Biochemistry,radioimmunoassay,and ELISA were used to detect the serum liver function,hepatic fibrosis index,MMP-1and TIMP-1levels.Results Compared with the model group,serum ALT,AST,TBIL,γ-GGT,HA,LN,Ⅳ-C and PCⅢlevels,MMP-1and the ratio of MMP-1/TIMP-1increased significantly and level of TIMP-1decreased significantly in Qishen Erlian Decoctiongroups,with statistical significance(P<0.05,P<0.01).And there is a certain dose-effect relationship,with Qishen Erlian Decoction high-dose group the best effect.Conclusion Qishen Erlian Decoction can improve the liver function and liver fibrosis indexes,regulate the level of MMP-1and TIMP-1,and prevent the progression of liver fibrosis.