24-乙酰泽泻醇A对ox-LDL诱导大鼠VSMC表型转化的影响及其与ERK1/2通路的关系
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国家自然科学基金面上项目(81473744),福建省卫生厅中医药科研项目(WZSY201304),福建省卫生系统中青年骨干人才培养项目(2013-ZQN-20-28)


The Effect of Alisol A 24-acetate on Phenotypic Modulation and the Correlation with ERK Pathway in ox-LDL-induced Rats Aorta Smooth Muscle Cells
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    摘要:

    目的 观察24-乙酰泽泻醇A(alisol A 24-acetate)对氧化型低密度脂蛋白(ox-LDL)诱导大鼠血管平滑肌细胞(VSMC)表型转化及其表型转化过程中合成基质金属蛋白酶9(MMP-9)能力的影响,并探讨与ERK1/2的相关性。方法 以酶消化法体外培养大鼠VSMC,ox-LDL(50 mg/L)进行诱导,24-乙酰泽泻醇A(10 mg/L)进行干预,免疫细胞化学染色观察VSMC收缩表型标记蛋白SM22α的变化;RT-PCR检测VSMC MMP-9 mRNA 的表达及Western blot检测VSMC MMP-9 和 ERK、p-ERK蛋白表达的变化。结果 在ox-LDL诱导下,VSMC收缩表型标志蛋白SM22α的表达降低,细胞向合成型转化,促进MMP-9的合成,伴随着ERK1/2磷酸化水平升高(P<0.05);在24-乙酰泽泻醇A的干预下,VSMC收缩表型标志蛋白SM22α的表达增加,细胞向收缩表型转化,伴随着MMP-9及p-ERK的表达下降(P<0.05)。结论 24-乙酰泽泻醇A能有效抑制VSMC表型转化和MMP-9的表达,其机制可能与抑制ERK1/2信号通路有关。

    Abstract:

    Aim To investigate the effect of alisol A 24-acetate on the phenotypic modulation of vascular smooth muscle cells(VSMC)as well as the expression of matrix metalloproteinase-9(MMP-9) in ox-LDL-induced rats vascular smooth muscle cells (VSMC), and their correlation with ERK1/2 pathway. Methods VSMC isolated from the thoracic aorta of rats were induced by ox-LDL(50 mg/L) and intervened by alisol A 24-acetate (10 mg/L). Immunocytochemistry was performed to detect the expression of SM22α protein.RT-PCR was performed to detect MMP-9 mRNA expression and Western blot was applied to detect the expressions of MMP-9, p-ERK and t-ERK. Results The contractive phenotypic specificity protein SM22α in the VSMC induced by ox-LDL was inhibited, VSMCs changed the phenotype from constriction to synthesis, the expression of phosphorylated ERK (p-ERK) and MMP-9 in ox-LDL group were elevated compared with the control group(P<0.05). Alisol A 24-acetate.partially inversed the effects of ox-LDL on VSMC (P<0.05). Conclusion Alisol A 24-acetate inhibited the phenotype transformation of VSMC induced by ox-LDL,and the mechanism maybe has correlation with ERK1/2 pathway.

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周晓茂,魏 伟, 陈 彤, 邓阳阳,薛偕华.24-乙酰泽泻醇A对ox-LDL诱导大鼠VSMC表型转化的影响及其与ERK1/2通路的关系[J].中国动脉硬化杂志,2015,23(04):342~346.

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  • 收稿日期:2014-10-29
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