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阿托伐他汀对家兔动脉粥样硬化VSMC凋亡的影响及其相关分子机制

发布时间:2018-11-13 10:14
【摘要】:目的分析家兔动脉硬化时大电导钙激活钾通道(BKCa)的表达以及阿托伐他汀干预后的变化,探讨阿托伐他汀对家兔动脉硬化血管平滑肌细胞(VSMC)凋亡的影响及其相关分子机制。方法家兔分为正常组、动脉粥样硬化组、阿托伐他汀组,HE染色观察家兔动脉粥样硬化病变,TUNEL检测VSMC凋亡并计算凋亡指数(AI),原位杂交法检测兔胸主动脉BKCaβ亚单位KCNMB1基因的表达,蛋白印迹法检测磷酸化细胞外信号调节激酶1/2(p-ERK1/2)的表达。结果动脉粥样硬化组胸主动脉内膜显著增厚,呈较典型的动脉粥样硬化病变;阿托伐他汀组VSMC凋亡指数较正常组、动脉粥样硬化组明显升高(36.51%±1.53%比6.80%±1.08%、27.83%±1.36%,P0.01);动脉粥样硬化组KCNMB1基因的表达较正常组明显下调(105.12±5.50比147.33±5.76,P0.01),而阿托伐他汀组KCNMB1基因的表达较动脉粥样硬化组明显增加(116.43±6.92比105.12±5.50,P0.01);阿托伐他汀组p-ERK1/2表达量低于动脉粥样硬化组(0.90±0.14比3.48±0.91,P0.01)。结论阿托伐他汀诱导动脉粥样硬化VSMC凋亡,该现象可能与其上调BKCa的KCNMB1基因表达及抑制ERK信号途径磷酸化有关。
[Abstract]:Objective to analyze the expression of calcium-activated potassium channel (BKCa) in rabbits with arteriosclerosis and the changes after intervention by Atto vastatin. To investigate the effect of Atto vastatin on (VSMC) apoptosis in rabbit arteriosclerotic vascular smooth muscle cells and its molecular mechanism. Methods Rabbits were divided into normal group, atherosclerosis group, Atto vastatin group, HE staining, VSMC apoptosis and (AI),. The expression of BKCa 尾 subunit KCNMB1 gene in rabbit thoracic aorta was detected by in situ hybridization, and the expression of extracellular signal regulated kinase 1 / 2 (p-ERK1/2) was detected by Western blot. Results the intima of thoracic aorta in atherosclerotic group was significantly thickened, showing typical atherosclerotic lesions. The VSMC apoptosis index in the Atto vastatin group was significantly higher than that in the normal group (36.51% 卤1.53% vs 6.80% 卤1.08% vs 27.83% 卤1.36P0.01). The expression of KCNMB1 gene in atherosclerosis group was significantly lower than that in normal group (105.12 卤5.50 vs 147.33 卤5.76 P0.01), while the expression of KCNMB1 gene in Atto vastatin group was significantly higher than that in atherosclerotic group (116.43 卤6.92 vs 105.12 卤5.50). P0.01); The expression of p-ERK1/2 in Atto vastatin group was lower than that in atherosclerotic group (0.90 卤0.14 vs 3.48 卤0.91 P0.01). Conclusion Atto vastatin induces apoptosis of atherosclerotic VSMC, which may be related to its up-regulation of KCNMB1 gene expression in BKCa and inhibition of ERK signal pathway phosphorylation.
【作者单位】: 广西医科大学第一附属医院心血管病研究所;
【基金】:广西自然科学基金项目(2010GXNSFA013175)
【分类号】:R543.5


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