依折麦布联合罗格列酮通过LXRα-ABCA1途径对血管平滑肌源性泡沫细胞胆固醇含量的影响
发布时间：2019-05-27 14:22
【摘要】：目的:研究依折麦布联合罗格列酮对氧化低密度脂蛋白(ox-LDL)诱导的血管平滑肌源性泡沫细胞胆固醇含量的影响,探讨肝X受体α(LXRα)-三磷酸腺苷结合盒转运体A1(ABCA1)信号通路在其中的作用。方法:正常培养的原代大鼠血管平滑肌细胞(VSMCs)作为空白对照组,利用ox-LDL(50ug/ml)干预VSMCs建立平滑肌源性泡沫细胞模型,然后根据实验要求将泡沫细胞分为泡沫细胞组、不同浓度的依折麦布组(3umol/L,10umol/L,30umol/L)、罗格列酮组(25umol/L)、联合组(30umol/L依折麦布+25 umol/L罗格列酮)。油红O染色鉴定泡沫细胞模型,real-time PCR检测各组细胞LXRα和ABCA1的m RNA表达,Western blot测定各组细胞LXRα和ABCA1蛋白表达,酶荧光法检测各组细胞内总胆固醇(TC)及游离胆固醇(FC)的含量。结果:1.与空白对照组相比,泡沫细胞组LXRα和ABCA1的m RNA表达降低(P0.05);与泡沫细胞组相比,不同浓度的依折麦布组LXRα和ABCA1的m RNA表达增加(P0.05),且呈一定浓度依赖性(P0.05)。2.与空白对照组相比,泡沫细胞组LXRα、ABCA1的m RNA和蛋白表达均降低(P0.05);与泡沫细胞组相比,依折麦布30umol/L组、罗格列酮组及联合组LXRα、ABCA1的m RNA和蛋白表达增加(P0.05),且联合组与依折麦布30umol/L组和罗格列酮组相比,LXRα、ABCA1的m RNA和蛋白表达增加更为显著(P0.05)。3.与空白对照组相比,泡沫细胞组细胞内TC、FC和胆固醇酯(CE)的含量均增加(P0.05),且CE/TC50%;与泡沫细胞组相比,依折麦布30umol/L组、罗格列酮组及联合组细胞内TC、FC、CE含量均减少,CE/TC比值下降(P0.05),且联合组与依折麦布30umol/L组和罗格列酮组相比,细胞内TC、FC、CE含量及CE/TC比值降低更为显著(P0.05)。结论:依折麦布及罗格列酮均可以通过上调LXRα-ABCA1信号通路,促进平滑肌源性泡沫细胞中ABCA1介导的胆固醇逆转运(RCT),减少细胞内蓄积的胆固醇;且两者联合可进一步上调LXRα和ABCA1的表达,促进胆固醇外流,显著降低细胞内胆固醇的含量。
[Abstract]:Objective: to study the effect of efolib combined with rosiglitazone on cholesterol content in vascular smooth muscle foam cells induced by oxidized low density lipoprotein (ox-LDL). To investigate the role of liver X receptor 伪 (LXR 伪)-adenosine triphosphate binding cassette transporter A1 (ABCA1) signaling pathway. Methods: the normal cultured primary rat vascular smooth muscle cells (VSMCs) were used as the blank control group. The smooth muscle foam cell model was established by the intervention of ox-LDL (50ug/ml) in VSMCs. According to the requirements of the experiment, foam cells were divided into foam cell group, different concentrations of ezumabe group (3umol group, 10umol group, 30umol group), rogaridone group (25umol/L), combined group (30umol/L etimab 25umol/L rosiglitazone). The foam cells were divided into foam cell group, different concentrations of ezumabe group (3umol group, 10umol group, 30umol group). The foam cell model was identified by oil red O staining. The expression of LXR 伪 and ABCA1 m RNA in each group was detected by real-time PCR. The expression of LXR 伪 and ABCA1 protein in each group was detected by, Western blot. The contents of total cholesterol (TC) and free cholesterol (FC) in each group were detected by enzyme fluorescence method. Result: 1. Compared with the blank control group, the expression of m RNA of LXR 伪 and ABCA1 in foam cell group was lower than that in blank control group (P 0.05). Compared with foam cell group, the expression of m RNA of LXR 伪 and ABCA1 in different concentrations of Ezumab group was increased (P 0.05), and the expression of m RNA was in a concentration dependent manner (P 0.05). Compared with the blank control group, the m RNA and protein expression of LXR 伪 and ABCA1 in foam cell group were decreased (P 0.05). Compared with foam cell group, the m RNA and protein expression of LXR 伪 and ABCA1 in ezumabe 30umol/L group, rosiglitazone group and combined group were increased (P 0.05), and the expression of m RNA and protein in combined group was higher than that in etumabe 30umol/L group and rosiglitazone group, and the expression of m RNA and protein in combined group was higher than that in etumabe group and rosiglitazone group. The expression of m RNA and protein in ABCA1 increased more significantly (P 0.05). Compared with the blank control group, the contents of TC,FC and cholesterol ester (CE) in foam cell group were increased (P 0.05), and the content of CE/TC50%; in foam cell group was higher than that in blank control group. Compared with foam cell group, the content of TC,FC,CE and the ratio of CE/TC in ezumabe 30umol/L group, rosiglitazone group and combination group were decreased (P 0.05), and the ratio of CE/TC in combined group was lower than that in etumabe 30umol/L group and rosiglitazone group. The intracellular TC,FC,CE content and CE/TC ratio decreased more significantly (P 0.05). Conclusion: both ezumab and rosiglitazone can up-regulate LXR 伪-ABCA1 signaling pathway and promote ABCA1-mediated reverse cholesterol transport (RCT), in smooth muscle-derived foam cells to reduce intracellular cholesterol accumulation. The combination of the two can further up-regulate the expression of LXR 伪 and ABCA1, promote cholesterol outflow, and significantly decrease the content of intracellular cholesterol.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R543.5
本文编号：2486218
[Abstract]:Objective: to study the effect of efolib combined with rosiglitazone on cholesterol content in vascular smooth muscle foam cells induced by oxidized low density lipoprotein (ox-LDL). To investigate the role of liver X receptor 伪 (LXR 伪)-adenosine triphosphate binding cassette transporter A1 (ABCA1) signaling pathway. Methods: the normal cultured primary rat vascular smooth muscle cells (VSMCs) were used as the blank control group. The smooth muscle foam cell model was established by the intervention of ox-LDL (50ug/ml) in VSMCs. According to the requirements of the experiment, foam cells were divided into foam cell group, different concentrations of ezumabe group (3umol group, 10umol group, 30umol group), rogaridone group (25umol/L), combined group (30umol/L etimab 25umol/L rosiglitazone). The foam cells were divided into foam cell group, different concentrations of ezumabe group (3umol group, 10umol group, 30umol group). The foam cell model was identified by oil red O staining. The expression of LXR 伪 and ABCA1 m RNA in each group was detected by real-time PCR. The expression of LXR 伪 and ABCA1 protein in each group was detected by, Western blot. The contents of total cholesterol (TC) and free cholesterol (FC) in each group were detected by enzyme fluorescence method. Result: 1. Compared with the blank control group, the expression of m RNA of LXR 伪 and ABCA1 in foam cell group was lower than that in blank control group (P 0.05). Compared with foam cell group, the expression of m RNA of LXR 伪 and ABCA1 in different concentrations of Ezumab group was increased (P 0.05), and the expression of m RNA was in a concentration dependent manner (P 0.05). Compared with the blank control group, the m RNA and protein expression of LXR 伪 and ABCA1 in foam cell group were decreased (P 0.05). Compared with foam cell group, the m RNA and protein expression of LXR 伪 and ABCA1 in ezumabe 30umol/L group, rosiglitazone group and combined group were increased (P 0.05), and the expression of m RNA and protein in combined group was higher than that in etumabe 30umol/L group and rosiglitazone group, and the expression of m RNA and protein in combined group was higher than that in etumabe group and rosiglitazone group. The expression of m RNA and protein in ABCA1 increased more significantly (P 0.05). Compared with the blank control group, the contents of TC,FC and cholesterol ester (CE) in foam cell group were increased (P 0.05), and the content of CE/TC50%; in foam cell group was higher than that in blank control group. Compared with foam cell group, the content of TC,FC,CE and the ratio of CE/TC in ezumabe 30umol/L group, rosiglitazone group and combination group were decreased (P 0.05), and the ratio of CE/TC in combined group was lower than that in etumabe 30umol/L group and rosiglitazone group. The intracellular TC,FC,CE content and CE/TC ratio decreased more significantly (P 0.05). Conclusion: both ezumab and rosiglitazone can up-regulate LXR 伪-ABCA1 signaling pathway and promote ABCA1-mediated reverse cholesterol transport (RCT), in smooth muscle-derived foam cells to reduce intracellular cholesterol accumulation. The combination of the two can further up-regulate the expression of LXR 伪 and ABCA1, promote cholesterol outflow, and significantly decrease the content of intracellular cholesterol.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R543.5
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