清肝活血方对酒精性肝纤维化大鼠基质金属蛋白酶的调控作用

作者	单位
郑培永	上海中医药大学龙华医院消化内科上海中医药大学脾胃病研究所
邢练军	上海中医药大学龙华医院消化内科上海中医药大学脾胃病研究所
王磊	上海中医药大学龙华医院消化内科上海中医药大学脾胃病研究所
季光	上海中医药大学龙华医院消化内科上海中医药大学脾胃病研究所
陈珺明	上海交通大学附属第六人民医院中医科

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中文摘要:

目的通过观察清肝活血方及其拆方对酒精性纤维化大鼠基质金属蛋白酶-2、9(MMP-2,9)和1型基质金属蛋白酶抑制物(TIMP-1)的调控作用,探讨清肝活血方及其拆方治疗酒精性肝纤维化的作用机制。方法雄性SD大鼠随机分为空白对照组、CCl4组(各10只)和造模组(110只)。造模组用白酒为主的复合因素进行干预。8周后造模组随机分为模型组(25只)、清肝活血方组、清肝方组及活血方组各15只,在实验第4、8、10周各取8只模型大鼠做病理分析以监测模型进展,余大鼠在造模中死亡。各治疗组分别加用相应药物灌胃,分别为4.75、1.50、3.25g/kg。12周末处死大鼠,采用蛋白印迹法、荧光定量PCR、免疫荧光法检测MMP-2、MMP-9、TIMP-1蛋白及mRNA表达。结果与空白对照组比较,模型组MMP-2、MMP-9、TIMP-1表达明显升高(1.81±0.28vs.0.53±0.04,1.60±0.16vs.0.45±0.05,1.20±0.02vs.0.35±0.07,P<0.01)。与模型组比较,清肝活血方及其拆方组TIMP-1表达均降低(0.56±0.05、0.67±0.02、0.70±0.02vs.1.20±0.02),MMP-2、MMP-9表达提高(4.18±0.53、2.70±0.40、2.38±0.22vs.1.81±0.28;3.31±0.06、2.56±0.20、1.87±0.05vs.1.60±0.16,P<0.05,P<0.01),全方组调控优于各拆方组(P<0.05,P<0.01)。结论清肝活血方及其拆方治疗酒精性肝纤维化的作用机制可能与调控MMP-2、9有关。

英文摘要:

Objective To study the action mechanism of Qinggan Huoxue Recipe(QGHXR) and its dissembled recipes for treatment of alcoholic liver fibrosis(ALF) by observing their regulation on the expressions of matrix metalloproteinases(MMPs) and type 1 tissue inhibitor of metalloproteinase(TIMP-1) . Methods 130 male SD rats were randomly divided into the blank control group(n=10) ,the CCl4 group(n=10) ,and the modeling group(n=110) . Rats in the modeling group were intervened by complex factors dominated as alcohol. Eight weeks later they were randomly divided into 4 subgroups,i.e.,the model group(n=25) ,the QGHXR group(n=15) ,the Qinggan Recipe(QGR) group(n=15) ,and the Huoxue Recipe(HXR) group(n=15) . Eight model rats were selected for pathological analysis to monitor the development of the modeling at the 4th,8th,and 10th week of the experiment. The rest rats died during the modeling. Corresponding medicines were given to these treatment groups(at the dose of 4.75 g/kg,1.50 g/kg,and 3.25 g/kg) . All rats were killed at the end of the 12th week. The protein and mRNA expressions of MMP-2,MMP-9,and TIMP-1 were detected using Western blotting,fluorescent quantitative polymerase chain reaction,and immumofluorescence method. Results Compared with the blank control group,the expressions of MMP-2,MMP-9,and TIMP-1 significantly increased in the model group(1.81±0.28 vs. 0.53±0.04,1.60±0.16 vs. 0.45±0.05,1.20±0.02 vs. 0.35±0.07,P<0.01) . Compared with the model group,QGHXR and its dissembled recipes all could decrease the protein and mRNA expressions of TIMP-1(0.56±0.05,0.67±0.02,0.70±0.02 vs. 1.20±0.02,P<0.05) ,increase the expressions of MMP-2 and MMP-9(4.18±0.53,2.70±0.40,2.38±0.22 vs. 1.81±0.28,3.31±0.06,2.56±0.20,1.87±0.05 vs. 1.60±0.16,P<0.05,P<0.01) . QGHXR was superior to its dissembled recipes(P<0.05,P<0.01) . Conclusion The action mechanisms of QGHXR and its dissembled recipes might possibly be correlated with regulating MMPs.

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