加味茵陈四逆汤对实验性肝纤维化小鼠MMP1和TIMPs表达的影响

Jiawei Yinchen Sini Decoction on MMP1 and TIMPs in Carbon Tetrachloride-Induced Hepatic Fibrosis Mice

目的:观察预防性使用加味茵陈四逆汤对肝纤维化小鼠肝组织中基质金属蛋白酶-1(MMP1)、基质金属蛋白酶抑制剂-1(TIMP1)和基质金属蛋白酶抑制剂-2(TIMP2)基因表达的影响。方法:将48只雄性ICR小鼠随机分为正常组、模型组、阳性对照组、中药高剂量组、中药中剂量组、中药低剂量组。30%CCl4(1.5 mg/kg,溶解于橄榄油)腹腔注射建立肝纤维化模型,同时给予药物灌胃处理。用药14 d后,各组行HE染色,观察肝脏病理组织学改变。RT-q PCR法检测MMP1、TIMP1和TIMP2 mRNA表达。结果:(1)病理结果显示模型组肝纤维化明显,中药高、中、低剂量组较模型组纤维化减轻;(2)MMP1 mRNA模型组表达量与正常组比较明显减少(P<0.05),与阳性药物组、中药中剂量和低剂量组相较表达量同样明显减少(P<0.05);(3)TIMP1 mRNA、TIMP2 mRNA模型组表达量比正常组明显增多(P<0.05),与阳性药物组和中药中、低剂量组相较均表达量减少(P<0.05)。结论:加味茵陈四逆汤可上调肝纤维化小鼠MMP1表达,抑制TIMP1、TIMP2表达,发挥对肝纤维化的抑制作用。

Objective： To observe the preventive effects of Jiawei Yinchen Sini Decoction（ JWYSN） on the gene expressions of MMP1,TIMP1 and TIMP2 in mice with hepatic fibrosis. Methods： Forty- eight male ICR mice were randomly divided into a normal group,a model group,a positive control group,JWYSN high,medium and low dose groups. The hepatic fibrosis model was established by intraperitoneal injection of 30% CCl4（ 1. 5 mg/kg,dissolved in olive oil）. Meanwhile,mice were treated with intragastric administration of drugs. After 14 days,the pathological fibrosis change was observed by performing HE staining. The mRNA expressions of MMP1,TIMP1 and TIMP2 were detected by RT- q PCR analysis. Results：（ 1） The pathological results showed hepatic fibrosis in the model group was significantly higher than that in JWYSN high,medium and low dose groups.（ 2） The expression of MMP1 mRNA in model group was obviously lower than the normal group（ P 〈 0. 05） as well as that of the positive control group,JWYSN medium and low dose groups（ P 〈 0. 05）.（ 3） Levels of TIMP1 mRNA and TIMP2 mRNA expressions increased significantly in model mice（ P 〈 0. 05） and expressions in positive control group,JWYSN medium and low dose groups were lower than that of the model group（ P 〈 0. 05）. Conclusion： Jiawei Yinchen Sini Decoction could up- regulate the expression of MMP1 mRNA and inhibit expressions of TIMP1 mRNA and TIMP2 mRNA in mice with hepatic fibrosis,and thus could attenuate the development of hepatic fibrosis.