氨氯地平对大鼠动脉粥样斑块稳定性和MMP-9及其抑制物表达的影响

Effect of amlodipine on the stability of atherosclerosis plague and the expression of MMP-9 and its inhibitor in mice

目的探讨氨氯地平对大鼠动脉粥样斑块稳定性和基质金属蛋白酶9(MMP-9)及其抑制物表达的影响。方法以18只雄性Wistar大鼠构建动脉粥样硬化模型,采用随机数字表法将18只雄性Wistar大鼠分为氨氯地平组和模型组,每组9只。模型组采取单纯高脂饲料喂养,氨氯地平组每日在高脂饮食基础上给予苯磺酸氯氨地平6 mg/(kg·d)灌胃。连续饲养3个月后采血检测血清总胆固醇(TC)、三酰甘油(TG);免疫组织化学SABC法进行MMP-9及基质金属蛋白酶组织抑制剂(TIMP-1)表达检测,同时计数血管平滑肌细胞(VSMC)和巨噬细胞占总细胞的百分比。结果氨氯地平组大鼠TC和TG水平分别为(1.63±0.74)mmol/L和(0.81±0.21)mmol/L,明显低于模型组的(3.08±0.67)mmol/L和(1.35±0.34)mmol/L,差异均有统计学意义(P<0.05);氨氯地平组MMP-9表达水平为(266.53±32.15)μm2,明显低于模型组的(351.02±45.69)μm2,TIMP-1表达水平为(305.64±36.22)μm2,明显高于模型组的(230.36±25.11)μm2,差异均有统计学意义(P<0.05);氨氯地平组血管平滑肌细胞[(88.12±3.58)%vs(100.00±0.00)%]和巨噬细胞[(90.35±5.33)%vs(100.00±0.00)%]占总细胞的百分比均显著低于模型组(P<0.05)。结论氨氯地平可抑制MMP-9的表达,进而起到稳定动脉粥样硬化板块、降低血脂的作用。

Objective To investigate the effect of amlodipine on the stability of atherosclerosis plague, and the expression of matrix metallopeptidase 9(MMP-9) and its inhibitor in mice. Methods The atherosclerosis model was built with 18 male Wistar rats, which were randomly divided into amlodipine group and model group, with 9 rats in each group.Rats in the model group was fed with high-fat diet, and those in amlodipine group were given gavage with 6 mg/(kg·d) amlodipine besylate on the basis of high-fat diet. Serum total cholesterol(TC), triglyceride(TG) were detected after continuous feeding for three months. MMP-9 and tissue inhibitor of metalloproteinase-1(TIMP-1) expression was detected by immunohistochemistry SABC method, and the percentage of vascular smooth muscle cells(VSMC) and macrophages in total cells were calculated. Results TC, TG levels in amlodipine group were significantly lower than those in model group [(1.63±0.74) mmol/L vs(3.08±0.67) mmol/L,(0.81±0.21) mmol/L vs(1.35±0.34) mmol/L, P<0.05]. The expression level of MMP-9 in amlodipine group was significantly lower than that in model group [(266.53 ± 32.15) μm2vs(351.02 ± 45.69) μm2, P<0.05], and the expression level of TIMP-1 in amlodipine group was significantly higher[(305.64±36.22) μm2vs(230.36±25.11) μm2, P<0.05]. The percentage of VSMC in total cells and the percentage of macrophages in total cells in amlodipine group were significantly lower than those in model group [(88.12 ± 3.58)% vs(100.00 ± 0.00)%,(90.35 ± 5.33)% vs(100.00 ± 0.00)%, P<0.05]. Conclusion Amlodipine can inhibit the expression of MMP-9, and thus play a stabilizing role in the atherosclerosis plate, which can also help reduce blood lipids.