糖尿病sLR11基因多态性与长期氧化应激及颈动脉IMT的关系

Diabetes mellitus patients with atherosclerosis are correlated with oxidation stress and polymorphism Gene. The correlation between Soluble low density lipoprotein receptor(sLR11) and atherosclerosis has become a hot spot of research in rencent years. Enhance of the Intracellular mitochondrial oxidative stress which was caused by hyperglycemia is a inevitable stage of Diabetes mellitus patients with atherosclerosis. Hyperglycemia is closely related with sLR11,but that mechanism is still not clear. In the cards,hyperglycemia induced the expression of.sLR11 by the Long-term control of oxidative stress which lead to the increase of sLR11 concentration,since,that will promote the development of the occurrence of atherosclerosis.We has yet to see the reports about the correlation between thesLR11 level ,gene polymorphism and long-term oxidative stress,early atherosclerosis.as well as national difference in the dibetes mellitus patients.This study investigates the correlation between sLR11 level,gene polymorphism and posterioritymtDNA A3243G somatic mutation rate as well as carotid IMT in the Korean and Han nationality Type 2 dibetes mellitus patients in YanBian District by TaqMan probe quantitative PCR and PCR-Taqman method as well as gene knock-out molecular biology technology .We clarify the correlation between the sLR11 level ,gene polymorphism and oxidative stress,early atherosclerosis.In addtion to ,we also clarify the mechanism of the atherosclerosis of diabetes patients.This provides theoretical basis for effectively preventing and controlling of diabetes early atherosclerosis.

糖尿病动脉硬化与氧化应激及基因多态性有关，可溶性低密度脂蛋白受体11（sLR11）与动脉硬化之间的相关性成为近年的研究热点。高血糖导致细胞线粒体内的氧化应激增加是糖尿病发生动脉硬化的必经阶段。高血糖与sLR11密切相关，但其机制尚不清楚。高血糖可能通过长期氧化应激调控诱导sLR11的表达，导致sLR11浓度升高，促进动脉硬化的发生发展。目前尚未见糖尿病sLR11水平、基因多态性与长期氧化应激及早期动脉硬化相关性研究及种族差异的报道。因此，本研究拟通过TaqMan probe定量PCR、PCR-Taqman及基因敲除等分子生物学技术，探讨延边地区朝汉族2型糖尿病sLR11水平及基因多态性与后天mtDNA A3243G体细胞变异率及颈动脉IMT的关系，阐明sLR11水平及基因多态性与长期.氧化应激及早期动脉硬化之间的相关性以及糖尿病动脉硬化的发生机制，为有效防治糖尿病早期动脉硬化提供理论。

糖尿病动脉硬化与氧化应激及基因多态性有关，可溶性低密度脂蛋白受体11（sLR11）与动脉硬化之间的相关性成为近年的研究热点。高血糖导致细胞线粒体内的氧化应激增加是糖尿病发生动脉硬化的必经阶段。高血糖与sLR11密切相关，但其机制尚不清楚。高血糖可能通过长期氧化应激调控诱导sLR11的表达，导致sLR11浓度升高，促进动脉硬化的发生发展。本研究通过TaqMan probe定量PCR法、PCR-Taqman技术、彩色多普勒等方法测定了延边地区朝鲜族、汉族2型糖尿病患者sLR11水平及基因多态性，分析后天mtDNA A3243G体细胞变异率与颈动脉IMT的关系，探讨sLR11水平及基因多态性与长期氧化应激及早期动脉硬化之间的相关性。研究结果表明，1.sLR11水平与空腹血糖、总胆固醇及甘油三酯呈正相关。sLR11基因rs3824968基因多态性可能通过上调LDL-C的浓度，促进T2DM的颈动脉粥样硬化的发生。2.sLR11基因rs641120野生纯合子CC是预防IMT增厚的保护性因子，当C→T突变时会增加CAS的发生3.后天的mtDNA3243A→G体细胞变异率与2型糖尿病及颈动脉粥样硬化有相关性。虽然在正常人群中尚未发现sLR11基因多态性与后天的mtDNA3243A→G体细胞变异率存在相关性，但sLR11基因rs3824968的T因子可能影响后天的mtDNA3243A→G体细胞变异率，增强2型糖尿病向颈动脉粥样硬化的迁移。4.sLR11基因rs689021、rs641120、rs668387存在连锁完全不平衡，rs641120可作为标签SNP。本研究进一步揭示了sLR11水平及基因多态性与2型糖尿病长期氧化应激及颈动脉硬化之间的相关性，为临床早期通过抗氧化治疗有效防治不同民族糖尿病患者大血管并发症提供基因学方面的理论依据。