阿司匹林和氟伐他汀对血管紧张素Ⅱ诱导的血管平滑肌细胞环氧合酶2表达的抑制作用
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Inhibition of AngiotensinⅡ-Induced Expression of Cyclooxygenase-2 by Aspirin and Fluvastatin in Human Vascular Smooth Muscle Cells
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    摘要:

    目的观察血管紧张素Ⅱ诱导的人脐动脉平滑肌细胞环氧合酶2的表达,并探讨阿司匹林和氟伐他汀的干预作用。方法培养人脐动脉平滑肌细胞,用不同浓度的血管紧张素Ⅱ作用细胞,观察环氧合酶2的表达;用不同浓度的阿司匹林、氟伐他汀或二者联用药物预处理细胞,观察血管紧张素Ⅱ诱导的环氧合酶2的表达。分别采用逆转录聚合酶链反应和细胞免疫化学染色法检测环氧合酶2mRNA和蛋白的表达。结果血管紧张素Ⅱ可诱导人脐动脉平滑肌细胞环氧合酶2mRNA的表达,且呈浓度依赖性,血管紧张素Ⅱ为1.0μmol/L时环氧合酶2表达最强;阿司匹林和氟伐他汀均可抑制血管紧张素Ⅱ对环氧合酶2的诱导,且随着药物浓度增大抑制作用增强;与单独应用阿司匹林或氟伐他汀比较,二者联合应用时血管紧张素Ⅱ诱导的环氧合酶2表达水平明显减低(p<0.05);细胞爬片免疫组织化学实验与以上结果符合。结论血管紧张素Ⅱ可诱导人血管平滑肌细胞环氧合酶2的表达,可能在动脉粥样硬化病变过程发挥重要作用;阿司匹林和他汀类药物抑制血管紧张素Ⅱ对环氧合酶2的诱导,且有协同抑制作用,为指导临床用药提出了新的思路。

    Abstract:

    Aim To observe the expression of angiotensinⅡ-induced cyclooxygenase-2 (COX-2) in cultured human umbilical vascular smooth muscle cells and investigate the influence of aspirin and fluvastatin on it. Methods Vascular smooth muscle cells were prepared from human umbilical arteries. The expression of COX-2 were observed in these cells after stimulated with different concentrations of angiotensinⅡ (AngⅡ) for 1 h, or stimulated with AngⅡ after treated with different concentrations of aspirin or fluvastatin or their combination for 1 h. Reverse transcription-polymerase chain reaction (RT-PCR) and cell immunocytochemistry were used for COX-2 mRNA and protein analysis. Results The expression of COX-2 mRNA was markedly increased under the stimulation of AngⅡ in a dose-dependent manner and reached to the peak when the concentration of AngⅡ was 1.0 μmol/L. This effect was inhibited by aspirin and fluvastatin, and the amount of COX-2 mRNA decreased gradually when the drugs dose increased. The amount of COX-2 mRNA was even lower in the drugs combination group than those in monotherapies groups (p<0.05). Results of the COX-2 protein expression with cell immunocytochemistry were coincident with those of mRNA expression with RT-PCR. Conclusions COX-2 can be induced by AngⅡ in cultured human vascular smooth muscle cells, which may play an important role in the progression of atherogenesis. Aspirin and fluvastatin can co-suppress the expression of COX-2, which may bring a novel therapeutic idea for drugs use.

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刘红梅,黄体钢,王林,甄琴,杨万松.阿司匹林和氟伐他汀对血管紧张素Ⅱ诱导的血管平滑肌细胞环氧合酶2表达的抑制作用[J].中国动脉硬化杂志,2007,15(3):193~196.

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  • 收稿日期:2006-09-14
  • 最后修改日期:2007-02-01
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