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目的研究血管紧张素Ⅱ(AngⅡ)对大鼠血管平滑肌细胞(VSMC)的增殖及基质金属蛋白酶-9(MMP-9)表达的影响及缬沙坦(Valsartan)的干预作用。方法分离大鼠胸主动脉平滑肌细胞,贴块法原代培养大鼠血管平滑肌细胞,取第5~10代细胞进行实验,随机分成AngⅡ组(A组)、AngⅡ+Valsartan组(A+V组)、Valsartan组(V组)及对照组4组,各组细胞分别采用四唑盐(MTT)比色法检测血管平滑肌细胞增殖,逆转录聚合酶链反应和免疫印迹法测定MMP-9mRNA和蛋白的表达水平。结果与对照组比较,AngⅡ组VSMC的增殖率升高;与AngⅡ组比较,AngⅡ+Valsartan组VSMC的增殖率降低,差异均明显(P<0.05)。AngⅡ组与对照组比较,MMP-9mRNA和蛋白的表达均升高;AngⅡ+Valsartan组与AngⅡ组比较,MMP-9mRNA和蛋白的表达均降低,差异均显著(P<0.05)。结论血管紧张素Ⅱ可以诱导血管平滑肌细胞的增殖和基质金属蛋白酶-9mRNA和蛋白的表达增加;血管紧张素Ⅱ1型受体(AT1R)拮抗剂-缬沙坦可抑制此作用,AT1R参与介导此过程。
Objective To investigate the effect of angiotensin Ⅱ (Ang Ⅱ) on the proliferation and the expression of matrix metalloproteinase-9 (MMP-9) in rat vascular smooth muscle cells (VSMC) and the effect of Valsartan on it. Methods Rat thoracic aorta smooth muscle cells were isolated and primary culture of rat vascular smooth muscle cells was performed by patch method. The cells in passage 5 to 10 were harvested and randomly divided into AngⅡ group (group A), Ang Ⅱ + Valsartan group (group A + V) ), Valsartan group (V group) and control group (4). The proliferation of vascular smooth muscle cells was detected by MTT colorimetric assay. The mRNA and protein of MMP-9 were determined by reverse transcription polymerase chain reaction The level of expression. Results Compared with the control group, the proliferation rate of VSMC in AngⅡgroup was increased. Compared with AngⅡgroup, the proliferation rate of VSMC in AngⅡ + Valsartan group decreased significantly (P <0.05). The expression of MMP-9 mRNA and protein in AngⅡgroup was higher than that in control group. The expression of MMP-9mRNA and protein in AngⅡ + Valsartan group was significantly lower than that in AngⅡgroup (P <0.05). Conclusion Angiotensin Ⅱ can induce the proliferation of vascular smooth muscle cells and increase the expression of MMP-9 mRNA and protein. Angiotensin Ⅱ type 1 receptor (AT1R) antagonist-valsartan can inhibit this effect. AT1R is involved in this process.