The present study was undertaken to investigate the effect of oxidized low density lipoprotein (oxLDL) on the expression of macrophage matrix metalloproteinase-12 (MMP-12), and the possible mechanisms. Activation of e...The present study was undertaken to investigate the effect of oxidized low density lipoprotein (oxLDL) on the expression of macrophage matrix metalloproteinase-12 (MMP-12), and the possible mechanisms. Activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was detected by Western blot Analysis. Enzymatic activity of MMP-12 was determined by β-casein zymography. RT-PCR analysis was used to measure the mRNA expression level of MMP-12. OxLDL-stimulated macrophages produced increased casein-degrading activities and oxLDL also significantly increased the mRNA level of MMP-12 in a dose-dependent manner. OxLDL stimulated the phosphorylation of ERK1/2 in macrophages. The use of the specific inhibitor indicated that the ERK1/2 signaling pathway was required for the induction of MMP-12. These data demonstrated that oxLDL induced MMP-12 expression in macrophages through an ERK1/2-dependent pathway. Key words oxidized low density lipoproteins - macrophage - matrix metalloproteinases CLC number Q 556+.9 Foundation item: Supported by the Natural Science Foundation of Hubei Province (99J138)Biography: He Chun-yan (1970-), female, Ph. D candidate, research direction: biochemistry diagnosis of atherosclerosis.展开更多
氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)在动脉粥样硬化(atherosclerosis AS)发病过程中的作用逐渐受到人们的重视。ox-LDL通过损伤内皮细胞、参与泡沫细胞形成、调控血管平滑肌的增殖等多个方面影响动脉粥样硬化...氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)在动脉粥样硬化(atherosclerosis AS)发病过程中的作用逐渐受到人们的重视。ox-LDL通过损伤内皮细胞、参与泡沫细胞形成、调控血管平滑肌的增殖等多个方面影响动脉粥样硬化的发生和发展。抗氧化剂的应用是治疗动脉粥样硬化的一个重要手段。展开更多
目的探讨三七总皂苷对动脉粥样硬化主动脉内皮的保护作用。方法载脂蛋白E基因敲除(apoE-KO)小鼠随机分为模型组、三七总皂苷组和辛伐他汀组,同种属C57BL/6J小鼠作为正常对照组。应用ELISA法测定小鼠血清氧化型低密度脂蛋白(oxLDL)含量,...目的探讨三七总皂苷对动脉粥样硬化主动脉内皮的保护作用。方法载脂蛋白E基因敲除(apoE-KO)小鼠随机分为模型组、三七总皂苷组和辛伐他汀组,同种属C57BL/6J小鼠作为正常对照组。应用ELISA法测定小鼠血清氧化型低密度脂蛋白(oxLDL)含量,透射电镜观察小鼠主动脉内皮细胞的超微结构。实时定量RT-PCR检测小鼠主动脉细胞分化抗原40(CD40)、血管细胞黏附分子-1(VCAM-1)mRNA表达水平。结果 apoE-KO小鼠的主动脉内皮和正常相比明显肿胀,连续性中断,可见细胞凋亡,胞核固缩,核内异染色质明显增多,线粒体空泡化。用药组内皮结构有不同程度的改善。与模型组相比,apoE-KO小鼠血清oxLDL水平显著升高(16.06ng/mL±4.16ng/mL vs 1.43ng/mL±0.84ng/mL,P<0.001),三七总皂苷及辛伐他汀均可显著降低apoE-KO小鼠血清oxLDL水平(4.45ng/mL±1.25ng/mL,3.92ng/mL±1.99ng/mL,P<0.001)。结论三七总皂苷对动脉粥样硬化小鼠血管内皮具有保护作用,其机制与降低血清oxLDL水平,下调主动脉CD40及VCAM-1的基因表达水平有关。展开更多
文摘The present study was undertaken to investigate the effect of oxidized low density lipoprotein (oxLDL) on the expression of macrophage matrix metalloproteinase-12 (MMP-12), and the possible mechanisms. Activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was detected by Western blot Analysis. Enzymatic activity of MMP-12 was determined by β-casein zymography. RT-PCR analysis was used to measure the mRNA expression level of MMP-12. OxLDL-stimulated macrophages produced increased casein-degrading activities and oxLDL also significantly increased the mRNA level of MMP-12 in a dose-dependent manner. OxLDL stimulated the phosphorylation of ERK1/2 in macrophages. The use of the specific inhibitor indicated that the ERK1/2 signaling pathway was required for the induction of MMP-12. These data demonstrated that oxLDL induced MMP-12 expression in macrophages through an ERK1/2-dependent pathway. Key words oxidized low density lipoproteins - macrophage - matrix metalloproteinases CLC number Q 556+.9 Foundation item: Supported by the Natural Science Foundation of Hubei Province (99J138)Biography: He Chun-yan (1970-), female, Ph. D candidate, research direction: biochemistry diagnosis of atherosclerosis.
文摘氧化低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)在动脉粥样硬化(atherosclerosis AS)发病过程中的作用逐渐受到人们的重视。ox-LDL通过损伤内皮细胞、参与泡沫细胞形成、调控血管平滑肌的增殖等多个方面影响动脉粥样硬化的发生和发展。抗氧化剂的应用是治疗动脉粥样硬化的一个重要手段。
文摘目的探讨三七总皂苷对动脉粥样硬化主动脉内皮的保护作用。方法载脂蛋白E基因敲除(apoE-KO)小鼠随机分为模型组、三七总皂苷组和辛伐他汀组,同种属C57BL/6J小鼠作为正常对照组。应用ELISA法测定小鼠血清氧化型低密度脂蛋白(oxLDL)含量,透射电镜观察小鼠主动脉内皮细胞的超微结构。实时定量RT-PCR检测小鼠主动脉细胞分化抗原40(CD40)、血管细胞黏附分子-1(VCAM-1)mRNA表达水平。结果 apoE-KO小鼠的主动脉内皮和正常相比明显肿胀,连续性中断,可见细胞凋亡,胞核固缩,核内异染色质明显增多,线粒体空泡化。用药组内皮结构有不同程度的改善。与模型组相比,apoE-KO小鼠血清oxLDL水平显著升高(16.06ng/mL±4.16ng/mL vs 1.43ng/mL±0.84ng/mL,P<0.001),三七总皂苷及辛伐他汀均可显著降低apoE-KO小鼠血清oxLDL水平(4.45ng/mL±1.25ng/mL,3.92ng/mL±1.99ng/mL,P<0.001)。结论三七总皂苷对动脉粥样硬化小鼠血管内皮具有保护作用,其机制与降低血清oxLDL水平,下调主动脉CD40及VCAM-1的基因表达水平有关。
