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机构地区:[1]武汉市第一医院,武汉市430020
出 处:《医学分子生物学杂志》2017年第3期147-151,共5页Journal of Medical Molecular Biology
基 金:武汉市卫计委课题(No.WXl6C38)
摘 要:目的探讨α-硫辛酸对兔动脉粥样硬化斑块形成及稳定性影响的机制。方法采用液氮冻伤术联合高脂饲料饲养构建兔动脉粥样硬化模型,并使用仅一硫辛酸处理动物2周,采用HE染色检测颈动脉组织的病理状态:ELISA检测给药前后兔血清中MMP-2和MMP-9的含量:Real-Time PCR和Western印迹检测给药后动脉组织中MMP-2和MMP-9的表达,并用Real-TimePCR检测组织中CDl47的mRNA表达。结果模型兔颈总动脉组织出现斑块,脂质沉积,泡沫细胞增多,炎性细胞浸润,α-硫辛酸能明显改善这种病理情况。模型兔血清中MMP-2和MMP-9的含量明显高于对照组(P〈0.05),α-硫辛酸处理2周后模型兔血清中MMP-2和MMP-9较模型组明显下降(P〈0.05)。各组动物动脉组织中MMP-2和MMP-9的mRNA和蛋白表达水平与血清中变化趋势一致,均具有显著差异(P〈0.05)。α-硫辛酸处理后动脉粥样硬化兔的动脉组织中CDl47的mRNA水平也较模型组明显下调(P〈0.05)。结论仪.硫辛酸可能是通过下调CDl47的方式来降低基质金属蛋白酶MMP-2和MMP-9的表达,最终改善兔动脉粥样硬化的进程。Objective To investigate the effects of α-lipoic acid on the formation and stability of atherosclerotic plaques in rabbits. Methods Atherosclerosis models of rabbits were established by liquid nitrogen frostbite combined with high fat diet. Animals were treated with α-lipoic acid for 2 weeks. The pathological changes of the carotid artery were observed by HE staining. The levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the serum of rabbits were detected before and after the administration by ELISA, the expressions of MMP-2, MMP-9 in the arterial tissues by re- al-time PCR and Western blotting, and the expression of CD147 in the arterial tissues by real-time PCR. Results Plaques were formed in the common carotid arteries of the model rabbits. Also, there were lipid deposition, increase of foam cells, and inflammatory cell infiltration. These patho- logical changes were greatly improved after treatment with α-lipoic acid. The levels of MMP-2 and MMP-9 were significantly higher in the serum of model rabbits than those in control group (P 〈 0. 05) ; they were profoundly decreased after α-lipoic acid treatment ( P 〈 0. 05 ). The changes of the mRNA and protein expression of MMP-2 and MMP-9 in arterial tissue were similar to those of se- rum levels of MMP-2 and MMP-9 (P 〈 0.05). The mRNA expression of CD147 in the arterial tis- sue of atherosclerotic rabbits after α-lipoic acid treatment was also significantly lower than that in model group (P 〈 0. 05). Conclusion α-lipoic acid inhibits the expression of MMP-2 and MMP-9 by down-regulating CD147, and ultimately improves the process of atherosclerosis in rabbits.
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