血清Nrf2、Keap1水平变化与糖尿病视网膜病变分期间关系

范存莉; 徐维诚; 陈玮; 翁月胜

doi:10.3969/j.issn.2096-3882.2024.01.007

血清Nrf2、Keap1水平变化与糖尿病视网膜病变分期间关系

如皋市中医院眼科, 江苏如皋 226500

基金项目:

南通市卫健委科研课题（QNZ2022066）

详细信息

中图分类号: R774.1
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- 文章访问数: 45
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出版历程
- 收稿日期: 2023-04-19
- 修回日期: 2023-09-24
- 网络出版日期: 2024-01-25

Relationship between serum Nrf2 and Keap1 levels and diabetic retinopathy staging

Department of Ophthalmology, Rugao Hospital of Traditional Chinese Medicine, Rugao, Jiangsu 226500, China

摘要

摘要: 目的探讨血清单核细胞核因子E2相关因子（Nrf2）、Kelch样ECH关联蛋白1（Keap1）水平变化与糖尿病视网膜病变（DR）分期间关系。方法选取2020年4月-2023年2月如皋市中医院DR患者147例作为观察组，并根据DR分期分为非增生型糖尿病视网膜病变（NPDR）、增生型糖尿病视网膜病变（PDR）；另选取同期糖尿病无视网膜病变患者49例作为对照Ⅰ组，健康体检者49例作为对照Ⅱ组。对比3组及观察组不同DR分期患者血清Nrf2、Keap1水平，Spearman秩相关系数分析血清Nrf2、Keap1水平与DR分期间关系；多因素logistic回归分析血清Nrf2、Keap1水平对DR分期的影响；限制性立方样条图分析血清Nrf2、Keap1水平与DR分期的剂量-效应关系。结果观察组血清Nrf2水平低于对照Ⅰ组、对照Ⅱ组，Keap1水平高于对照Ⅰ组、对照Ⅱ组，对照Ⅰ组血清Nrf2水平低于对照Ⅱ组，Keap1水平高于对照Ⅱ组（P<0.05）；随DR分期增加，血清Nrf2水平呈降低趋势，血清Keap1水平呈升高趋势（P<0.05）；血清Nrf2水平与DR分期呈负相关（r=-0.806，P<0.001），血清Keap1水平与DR分期呈正相关（r=0.854，P<0.001）；经多因素logistic回归分析，高血压、糖尿病发病年龄、总胆固醇对DR分期无显著影响（P>0.05），血清Nrf2水平是DR分期的独立保护因素，高脂血症、糖尿病病程、空腹血糖、糖化血红蛋白、血清Keap1水平是DR分期的独立危险因素（P<0.05）；限制性立方样条图分析显示，血清Nrf2（χ²=11.800，P<0.001）、Keap1（χ²=8.401，P=0.015）水平与DR分期间存在非线性关系，控制其他病变为固定变量，血清Nrf2水平<1.70 μg/L、血清Keap1水平>3.00 μg/L时，PDR风险显著增加。结论血清Nrf2、Keap1水平变化与DR分期关系密切，血清Nrf2水平<1.70 μg/L、血清Keap1水平>3.00 μg/L时提示DR进展至PDR的风险显著增加。
- 糖尿病视网膜病变 /
- 单核细胞核因子E2相关因子 /
- Kelch样ECH关联蛋白1 /
- 增生型糖尿病视网膜病变 /
- 限制性立方样条图
Abstract: Objective To investigate the relationship between the levels of serum mononuclear nuclear factor E2 associated factor (Nrf2) and Kelch-like ECH associated protein 1 (Keap1) and diabetic retinopathy (DR) staging. Methods A total of 147 DR patients who were admitted to Rugao Traditional Chinese Medicine Hospital from April 2020 to February 2023 were selected as an observation group. According to DR staging, they were divided into two types:non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). Meanwhile, 49 diabetic patients without retinopathy were selected as a control Ⅰ group, and 49 healthy patients were selected as a control Ⅱ group. These groups were compared for the levels of serum Nrf2 and Keap1. The relationship between serum Nrf2 and Keap1 levels and DR staging was analyzed by Spearman rank correlation coefficient. The effect of serum Nrf2 and Keap1 levels on DR staging was analyzed by multivariate logistic regression. The dose-effect relationship between serum Nrf2 and Keap1 levels and DR staging was analyzed by restricted cubic spline diagram. Results The observation group showed lower levels of serum Nrf2 but higher levels of serum Keap1 than the control Ⅰ and Ⅱ groups, while the control Ⅰ group presented lower levels of serum Nrf2 but higher levels of serum Keap1 than control Ⅱ group (P<0.05). With the increase of DR stages, serum Nrf2 levels decreased, but serum Keap1 levels increased (P<0.05). Serum Nrf2 levels were negatively correlated with DR staging (r=-0.806, P<0.001), while serum Keap1 levels were positively correlated with DR staging (r=0.854, P<0.001). According to multiple logistic regression analysis, hypertension, diabetes onset age and total cholesterol exerted no significant effect on DR staging (P>0.05). Serum Nrf2 level was an independent protective factor for DR staging, while hyperlipidemia, diabetes course, fasting blood glucose, glycosylated hemoglobin and serum Keap1 level were independent risk factors for DR staging (P<0.05). Restricted cubic spline analysis indicated a nonlinear relationship between serum Nrf2 (χ²=11.800, P<0.001), Keap1 (χ²=8.401, P=0.015) levels and DR staging; the risk of PDR significantly increased when other diseases were controlled as fixed variables, while serum Nrf2 levels were lower than 1.70 μg/L and serum Keap1 levels were higher than 3.00 μg/L. Conclusions Serum Nrf2 and Keap1 levels are closely related to DR staging. Serum Nrf2 level < 1.70 μg/L and serum Keap1 level > 3.00 μg/L suggest a significantly increased risk of progression from DR to PDR.
- diabetic retinopathy /
- factors related to mononuclear nuclear factor E2 /
- kelch-like ECH associated protein 1 /
- proliferative diabetic retinopathy /
- restricted cubic spline graph

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