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阿托伐他汀對(duì)家兔動(dòng)脈粥樣硬化VSMC凋亡的影響及其相關(guān)分子機(jī)制

發(fā)布時(shí)間:2018-11-13 10:14
【摘要】:目的分析家兔動(dòng)脈硬化時(shí)大電導(dǎo)鈣激活鉀通道(BKCa)的表達(dá)以及阿托伐他汀干預(yù)后的變化,探討阿托伐他汀對(duì)家兔動(dòng)脈硬化血管平滑肌細(xì)胞(VSMC)凋亡的影響及其相關(guān)分子機(jī)制。方法家兔分為正常組、動(dòng)脈粥樣硬化組、阿托伐他汀組,HE染色觀察家兔動(dòng)脈粥樣硬化病變,TUNEL檢測(cè)VSMC凋亡并計(jì)算凋亡指數(shù)(AI),原位雜交法檢測(cè)兔胸主動(dòng)脈BKCaβ亞單位KCNMB1基因的表達(dá),蛋白印跡法檢測(cè)磷酸化細(xì)胞外信號(hào)調(diào)節(jié)激酶1/2(p-ERK1/2)的表達(dá)。結(jié)果動(dòng)脈粥樣硬化組胸主動(dòng)脈內(nèi)膜顯著增厚,呈較典型的動(dòng)脈粥樣硬化病變;阿托伐他汀組VSMC凋亡指數(shù)較正常組、動(dòng)脈粥樣硬化組明顯升高(36.51%±1.53%比6.80%±1.08%、27.83%±1.36%,P0.01);動(dòng)脈粥樣硬化組KCNMB1基因的表達(dá)較正常組明顯下調(diào)(105.12±5.50比147.33±5.76,P0.01),而阿托伐他汀組KCNMB1基因的表達(dá)較動(dòng)脈粥樣硬化組明顯增加(116.43±6.92比105.12±5.50,P0.01);阿托伐他汀組p-ERK1/2表達(dá)量低于動(dòng)脈粥樣硬化組(0.90±0.14比3.48±0.91,P0.01)。結(jié)論阿托伐他汀誘導(dǎo)動(dòng)脈粥樣硬化VSMC凋亡,該現(xiàn)象可能與其上調(diào)BKCa的KCNMB1基因表達(dá)及抑制ERK信號(hào)途徑磷酸化有關(guān)。
[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% 鹵1.53% vs 6.80% 鹵1.08% vs 27.83% 鹵1.36P0.01). The expression of KCNMB1 gene in atherosclerosis group was significantly lower than that in normal group (105.12 鹵5.50 vs 147.33 鹵5.76 P0.01), while the expression of KCNMB1 gene in Atto vastatin group was significantly higher than that in atherosclerotic group (116.43 鹵6.92 vs 105.12 鹵5.50). P0.01); The expression of p-ERK1/2 in Atto vastatin group was lower than that in atherosclerotic group (0.90 鹵0.14 vs 3.48 鹵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.
【作者單位】: 廣西醫(yī)科大學(xué)第一附屬醫(yī)院心血管病研究所;
【基金】:廣西自然科學(xué)基金項(xiàng)目(2010GXNSFA013175)
【分類號(hào)】:R543.5
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