芪参益气滴丸对DMN大鼠肝纤维化及肝组织TIMP-1表达的影响

Effects of Chinese herbs compound Qishenyiqi pills on expression of TIMP-1 in fibrotic liver induced by dimethylnitrosamine in rats

目的：应用二甲基亚硝胺(DMN)建立肝纤维化大鼠模型,研究芪参益气滴丸对纤维化肝组织中TIMP-1表达的影响。方法：60只大鼠随机分为正常对照组、6 wk模型组、芪参益气滴丸干预组(干预组)、10 wk模型组及芪参益气滴丸治疗组(治疗组)。采用DMN腹腔内注射的方法建立肝纤维化大鼠模型。按6期分类法评价各组肝纤维化程度。应用RT-PCR检测各组肝组织中TIMP-1 mRNA水平；应用免疫组织化学技术检测各组动物肝组织TIMP-1的表达。结果：芪参益气滴丸干预组与治疗组的大鼠肝纤维化程度分别较6 wk模型组与10 wk模型组显著减轻(P<0．01)。干预组与治疗组肝组织中TIMP-1 mRNA水平分别较6 wk模型组与10 wk模型组显著下降(P<0．01),TIMP-1的阳性表达均分别较6 wk模型组与10 wk模型组显著减弱(P<0．05,P<0．01)。结论：芪参益气滴丸能明显改善纤维化肝组织病理改变和减轻肝纤维化程度,抑制TIMP-1的表达是其抗肝纤维化的机制之一。

AIM： To investigate the effect of Chinese herbs compound Qishenyiqi pills on expressions of TIMP-1 in the fibrotic liver induced by dimethylnitrosamine （DMN） in rat model. METHODS： Sixty Wistar rats were randomly divided into normal control group, 6-wk model group, Qishenyiqi pills intervened group, 10-wk model group, and Qishenyiqi pills therapeutic group. The rat models of liver fibrosis were induced by intraperitoneal injection of DMN. According to 6 staging classification, liver fibrosis grades were evaluated on the liver tissue sections performing with HE and Reticulation＇s stain. Semi-quantitive RT-PCR was performed to determine mRNA levels of TIMP-1 in liver tissues. Immunohistochemical staining was utilized to show the positive expression of TIMP-1 in liver tissues. RESULTS： Comparing with 6-wk model group, grade of liver fibrosis in Qishenyiqi pills intervened group was obviously lower （P 〈 0.01 ） ; furthermore comparing with 10-wk model group, the liver fibrosis was significantly reduced after therapy of Qishenyiqi pills （P 〈 0.01 ）. In intervened and therapeutic groups, the liver tissue mRNA levels of collagen TIMP-1 were all obviously lower than those in 6-wk model and 10-wk model groups respectively （P 〈 0.01 ） and the positive expressions of TIMP-1 in liver tissues were much weaker than those in 6-wk model and 10-wk model groups respectively （P 〈 0.05, P 〈 0.01 ） . CONCLUSION： Qishenyiqi pills has positively preventive and therapeutic effects on the experimental liver fibrosis induced by DMN in rats. Inhibiting the expression of TIMP-1 in liver tissue is one of the anti-fibrosis mechanisms of Qishenyiqi pills.