摘要
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。
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,PCⅢand 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.
作者
程小丽
赵余珠
王志旺
丁茂鹏
韦凌霞
潘虹
CHENG Xiao-li;ZHAO Yu-zhu;WANG Zhi-wang;DING Mao-peng;WEI Ling-xia;PAN Hong(Gansu University of Chinese Medicine,Lanzhou 730000;Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730000,China)
出处
《中国应用生理学杂志》
CAS
CSCD
北大核心
2020年第5期499-502,共4页
Chinese Journal of Applied Physiology
基金
国家自然科学基金(81860787)
甘肃省教育厅基金项目(2015A-096)。
