【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%,P<0.01);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,P<0.01),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,P<0.01);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,P<0.01)。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。更多还原

【Abstract】 Aim To analyze the expression of calcium activated potassium channel( BKCa),phosphorylated extracellular signal regulated kinase 1/2( p-ERK1/2) and apoptosis in vascular smooth muscle cells( VSMC) from rabbits with atherosclerosis before and after atorvastatin treatment,and to discuss whether atorvastatin-induced VSMC apoptosis in rabbits with atherosclerosis is associated with BKCa upregulation and ERK signaling pathway inhibition. Methods Experimental rabbits were divided into normal group,atherosclerosis group and atorvastatin group. Tissue samples were taken and rabbit atherosclerotic lesions were observed by HE staining,TUNEL assay was used to measure the apoptosis of VSMC,q PCR and Western blot were performed for detection of rabbit aortic BKCa KCNMB1 mRNA and p-ERK1/2 protein,respectively. Results In atherosclerosis group,the intima of thoracic aorta was significantly thickened,showing typical atherosclerotic lesions. The apoptotic index of VSMC in atorvastatin group was significantly higher than that in normal group and atherosclerosis group( 36.51% ±1.53% vs. 6.80% ±1.08% and 27.83% ±1.36%,P<0.01). The KCNMB1 mRNA expression in atherosclerosis group was significantly lower than that in normal group( 105. 12 ± 5. 50 vs. 147. 33 ±5.76,P<0. 01),while the KCNMB1 mRNA expression in atorvastatin group was significantly higher than that in atherosclerosis group( 116.43±6.92 vs. 105. 12 ± 5. 50,P < 0. 01). Phosphorylation of ERK1/2 in atorvastatin group was lower than that in atherosclerosis group( 0.90±0.14 vs. 3.48±0.91,P< 0.01). Conclusion Atorvastatin can induce VSMC apoptosis,which may be related to the upregulation of KCNMB1 gene expression and the inhibition of phosphorylation of ERK signaling pathway.更多还原