卡托普利对肝纤维化模型鼠MMP-2,3 TIMP-2,3表达的影响

Effects of captopril on expression of MMP-2, 3 and TIMP-2, 3 in rat hepatic fibrosis

目的:探讨卡托普利抗大鼠肝纤维化的作用及对MMP-2,MMP-3,TIMP-2,TIMP-3的表达影响。方法:Wistar大鼠40只随机分为正常对照组,实验对照组A、B,卡托普利预防组、治疗组,采用混合损害因素构建肝纤维化模型。行HE和VG染色,判断炎症和肝纤维化程度,免疫组化检测MMP-2,MMP-3,TIMP-2,TIMP-3的表达。结果:实验对照组A平均肝纤维化积分值为2.17±0.75、卡托普利预防组为1.33±0.52;实验对照组B为2.86±0.69、卡托普利治疗组为1.67±0.82,二者比较均P<0.05。实验对照组A、卡托普利预防组的MMP-2阳性反应面积比分别为8.20±0.24％,4.43±0.25％,实验对照组B、治疗组分别为5.67±0.32％,3.21±0.16％,二者比较均P<0.01;实验对照组A、卡托普利预防组MMP-3阳性反应面积比分别为1.54±0.36％,4.25±0.37％,实验对照组B、治疗组分别为3.69±0.27％,10.75±1.69％,二者比较均P<0.01;实验对照组A、卡托普利预防组TIMP-2阳性反应面积比分别为3.61±0.46％,2.16±0.17％,实验对照组B、治疗组分别为6.68±0.52％,7.87±0.59％,二者比较均P<0.01;实验对照组A、卡托普利预防组TIMP-3阳性反应面积比分别为4.13±0.29％,3.06±0.28％,实验对照组B、治疗组分别为8.54±0.45％,5.35±0.34％,二者比较均P<0.01。结论:卡托普利可抑制MMP-2,TIMP-3蛋白表达,增强MMP-3蛋白表达,可能是其抗纤维化作用的机制之一。

AIM: To investigate the effects of captopril on the expression of MMP-2,3 and TIMP-2, 3 in rat hepatic fibrosis. METHODS: Forty healthy Mistar rats were randomly divided into five groups: normal control group, experiment group A,experiment group B, captopril-prevention group, captopril- treatment group. Hepatic fibrosis models were induced in the latter 4 groups by a combination of several factors. Liver sections were stained by hematoxylin-eosin and Van Gieson to evaluate the degree of inflammation and hepatic fibrosis. Expression of MMP-2, 3 and TIMP-2, 3 in liver were assayed by immunohistochemistry. RESULTS: There was significant difference between captopril-prevention group(1.33±0.52)and experimental group A (2.17±0.75) on histologic assessment of hepatic fibrosis, and between captopril-treated group (1.67±0.82) and experimental group B (2.86±0.69) (P<0.05). The ratios of positive expression area of MMP-2 in captopril-prevention group and captopril-treatment group (4.43±0.25 % and 3.21±0.16 %, respectively) was smaller than in experimental group A and B (8.20±0.24 % and 5.67±0.32 %, respectively), (P<0.01). Expression of MMP-3 in experimental group A and experimental group B (1.54±0.36 % and 3.69±0.27 %, respectively) was weaker than in captopril-prevention group and captopril-treated group (4.25±0.37 % and 10.75±1.69 %, respectively) (P<0.01). Expression of TIMP-2 in captopril- prevention group (2.16±0.17 %) was weaker than in ex- perimental group A (3.61±0.46 %) (P<0.01); but TIMP-2 in captopril-treatment group (7.87±0.59 %) was stronger than in experimental group B (6.68±0.52 %) (P<0.01). Expression of TIMP-3 in captopril-prevention group and captopril-treatment group (3.06±0.28 % and 5.35±0.34 %, respectively) was weaker than in experimental group A and experimental group B(4.13±0.29 % and 8.54±0.45 %, respectively) (P<0.01). CONCLUSION: Captopril could suppress expression of MMP-2, TIMP-3, and enhance the expression of MMP-3, which might be related with its anti-hepatic fibrosis activity.