作　　者： ;

机构地区： 南方医科大学第三附属医院

出　　处： 《南方医科大学学报》 2018年第8期980-985,共6页

摘　　要： 目的观察槲皮素对氧化型低密度脂蛋白(Ox-LDL)诱导的血管平滑肌细胞成骨样分化和钙化的作用,并阐明其分子机制。方法采用Ox-LDL处理人血管平滑肌细胞,茜素红染色检测细胞钙化,测定碱性磷酸酶(ALP)活性和q PCR测骨相关蛋白Msx2、BMP2、Osterix以及收缩蛋白SMA和SM22αm RNA表达水平。观察槲皮素对Ox-LDL诱导的血管平滑肌细胞钙化,ALP活性,TLR4、Msx2、BMP2、Osterix、SMA和SM22α的m RNA表达水平,ROS含量及SOD活性的影响。采用TLR4 si RNA转染血管平滑肌细胞,观察敲低TLR4对细胞钙化,ALP活性及Msx2、BMP2、Osterix、SMA和SM22αm RNA表达水平的影响。结果 Ox-LDL可促进血管平滑肌细胞钙化和上调TLR4表达水平(P<0.05);槲皮素能明显减轻Ox-LDL诱导的细胞钙化和降低ALP的活性,下调Msx2、BMP2、Osterix m RNA的表达水平,上调血管平滑肌收缩蛋白SMA和SM22αm RNA的表达水平(P<0.05)。此外,槲皮素可明显提高SOD的活性,降低活性氧物质(ROS)的含量,下调TLR4的表达水平(P<0.05);TLR4 si RNA也能减轻Ox-LDL诱导的细胞钙化(P<0.05)。结论槲皮素可明显抑制Ox-LDL诱导的血管平滑肌细胞钙化,其机制可能与ROS激活的TLR4信号通路有关。 Objective To determine whether quercetin inhibits oxidized low-density lipoprotein（Ox-LDL）-induced osteogenic differentiation and calcification of vascular smooth muscle cells（VSMCs） and understand the underlying mechanism.Methods The calcification of human VSMCs following Ox-LDL treatment was assessed using alizarin red staining and by detecting ALP activity. The m RNA expressions of the bone-related genes including Msx2, BMP2 and Osterix, and the contractile proteins including SMA and SM22α were analyzed using q PCR. The effects of quercetin were investigated on OxLDL-induced VSMC calcification and changes in ALP activity, expressions of Msx2, BMP2, Osterix, SMA and SM22α, ROS levels and SOD activity. The effect of Toll like receptor 4（TLR4） silencing mediated by si RNA transfection on cell calcification,ALP activity, gene expressions and ROS levels were investigated. Results Ox-LDL treatment promoted VSMC calcification and up-regulated TLR4 expression. Quercetin treatment significantly attenuated Ox-LDL-induced VSMC calcification, reduced ALP activity, down-regulated the expression levels of Msx2, BMP2 and Osterix, and up-regulated the expressions of vascular smooth muscle contractile proteins SMA and SM22α. In addition, Quercetin treatment markedly increased SOD activity,reduced ROS levels and TLR4 expression in VSMCs. Silencing TLR4 expression using TLR4 si RNA also significantly decreased calcification of the VSMCs. Conclusion Quercetin inhibits Ox-LDL-induced VSMC calcification in VSMCs possibly by targeting the ROS/TLR4 signaling pathway.

关 键 词： 血管钙化 血管平滑肌细胞 槲皮素 成骨样分化 氧化型低密度脂蛋白

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