血清同型半胱氨酸水平与外周血中FOXO1DNA甲基化在糖尿病视网膜病变中的关联性研究  

The Correlation Study of Serum Homocysteine Levels and FOXO1 DNA Methylation in Diabetic Retinopathy

作　　者：高春兰[1,2] 张辉[2] 邹晓燕[1] 张鑫[1] 郑白兰[1] 李红莉[1] 姜怡邓[2] 

机构地区：[1]宁夏银川市第一人民医院,银川750001 [2]宁夏医科大学,银川750004

出　　处：《宁夏医科大学学报》2016年第12期-,共5页Journal of Ningxia Medical University

基　　金：宁夏自然科学基金(NZ14238)

摘　　要：目的研究糖尿病视网膜病变(DR)患者血清中同型半胱氨酸(Hcy)和外周血中叉头状转录因子O1(FOXO1)DNA甲基化水平,为深入探讨DR的发生机制和靶向性治疗提供实验依据。方法收集2013年1月-2016年3月宁夏银川市第一人民医院眼科和内分泌科门诊及住院的2型糖尿病(DM)患者资料,根据是否伴有视网膜病变分为2组:无视网膜并发症患者作为DM组,DR患者为DR组,检测患者血清中Hcy水平、糖化血红蛋白含量、外周血中FOXO1 m RNA表达水平,并采用甲基化特异性PCR技术分析FOXO1 DNA甲基化水平,分析Hcy与FOXO1 DNA甲基化的相关性。结果一般资料分析可见DR组患者病程较长,血清Hcy水平显著升高。与DM组相比,在DR组中FOXO1 m RNA表达升高了3.25倍,差异具有统计学意义(P<0.01)。DR患者外周血中FOXO1 DNA甲基化水平显著下降,与DM组相比下降了51.23%,差异具有统计学意义(P<0.01)。Hcy与FOXO1 DNA甲基化水平呈负相关(r2=-0.4833,P=0.0016)。结论 Hcy可能通过下调FOXO1 DNA甲基化水平上调了FOXO1的表达而参与DR的发生发展,可能成为靶向性治疗DR的潜在靶点。Objective To investigate the levels of homocysteine(Hcy)in serum andFOXO1 DNA methylation levels in patients of diabetic retinopathy(DR)and to provide experiment evidences for further exploring the mechanisms of DR developing and target therapy for DR.Methods Subjects were divided into two groups: DM group without diabetic retinopathy and DR group with diabetic retinopathy. The Hcy levels and glycosylated hemoglobin content in peripheral blood of patients with diabetes were measured in January 2013 to March 2016 in Ningxia Yinchuan First People's Hospital. Real time PCR was used to detectFOXO1 mRNA levels,andFOXO1 DNA methylation levels were analyzed with methylation specific PCR technology analysis. The relationship of Hcy andFOXO1 DNA methylation in peripheral blood were analyzed.Results General data analysis presented that the course of the disease was significantly longer in DR group. Hcy content in serum andFOXO1 mRNA levels significantly increased in DR group compared with diabetic group(P<0.01).FOXO1 DNA methylation levels significantly decreased in DR group compared with diabetic group(P<0.01). There was a significantly negative correlation between Hcy withFOXO1 DNA methylation level(r2=-0.4833,P=0.0016).Conclusion Hcy may took part in the developing of DR by decreasingFOXO1 expression,through which Hcy suppressedFOXO1 DNA methylation level. These findings may provide an potential therapy target for DR.

关 键 词：糖尿病视网膜病变 同型半胱氨酸 叉头状转录因子O1 DNA甲基化 

分 类 号：R587.2[医药卫生—内分泌] R774.1[医药卫生—内科学]