糖尿病性视网膜病变患者血清microRNA-20a-5p、VEGF水平变化及其临床意义

Changes of serum microRNA-20a-5p and VEGF levels in patients with diabetic retinopathy and their clinical significance

摘要:

目的 探讨糖尿病性视网膜病变（DR）患者血清microRNA-20a-5p（miR-20a-5p）、血管内皮生长因子（VEGF）水平变化及其临床意义。方法 选取遵义市第一人民医院眼科2018年1月—2020年12月收治的82例DR患者为DR组，根据DR严重程度分为增殖型糖尿病性视网膜病变（PDR）组（n =27）和非增殖型糖尿病性视网膜病变（NPDR）组（n =55）。选取同期单纯T2DM患者为T2DM组，42例体检健康者为对照组。采用实时荧光定量聚合酶链反应（qRT-PCR）检测各组血清miR-20a-5p mRNA相对表达量；采用酶联免疫吸附试验（ELISA）检测血清VEGF水平；采用葡萄糖氧化酶法测定空腹血糖（FBG）、胶乳凝集反应法测定糖化血红蛋白（HbA1c）水平。Pearson相关性分析DR患者血清miR-20a-5p mRNA相对表达量与VEGF、FBG、HbA1c的相关性，多因素Logistic回归分析血清miR-20a-5p、VEGF与DR发生的关系，ROC曲线分析血清miR-20a-5p、VEGF对DR发生的预测价值。结果 与T2DM组比较，DR组FBG、HbA1c、VEGF水平升高，血清miR-20a-5p mRNA相对表达量降低，与对照组比较，T2DM组FBG、HbA1c、VEGF水平升高，血清miR-20a-5p mRNA相对表达量降低（P <0.05）。与NPDR组比较，PDR组FBG、HbA1c、VEGF水平升高，血清miR-20a-5p mRNA相对表达量降低（P <0.05）。DR患者血清miR-20a-5p mRNA相对表达量与FBG、HbA1c、VEGF水平呈负相关（r =-0611、-0.799和-0.545，均P <0.05）。多因素Logistic回归分析显示，血清miR-20a-5p高水平［O^R=0.254（95% CI：0.154，0.596）］为DR发生的独立保护因素，糖尿病病程长［O^R=2.042（95% CI：1.422，2.933）］、血清HbA1c高水平［O^R=2.307（95% CI：1.101，4.833）］、血清VEGF高水平［O^R=2.570（95% CI：1.584，4.144）］为DR发生的独立危险因素（P <0.05）。ROC曲线显示，血清miR-20a-5p预测DR发生敏感性为97.56%（95% CI：0.915，0.997）、特异性为61.54%（95% CI：0.471，0.748）；血清VEGF敏感性为57.32%（95% CI：0.447，0.683）、特异性为96.15%（95% CI：0.868，0.995）；联合预测敏感性为91.46%（95% CI：0.832，0.965）、特异性为76.92%（95% CI：0.632，0.875）。结论 DR患者血清miR-20a-5p mRNA相对表达量降低，与FBG、HbA1c、VEGF水平密切相关，miR-20a-5p可能通过调控糖代谢和VEGF介导DR发生和发展。

Abstract:

Objective To investigate the changes of serum microRNA-20a-5p (miR-20a-5p) and vascular endothelial growth factor (VEGF) levels in patients with diabetic retinopathy (DR) and their clinical significance.Methods From January 2018 to December 2020, 82 patients with DR admitted to Department of Ophthalmology, Zunyi First People's Hospital were selected as the DR group, who were divided into a proliferative retinopathy (PDR) group (n = 27) and a non-proliferative retinopathy (NPDR) group (n = 55) based on proliferation. Patients with T2DM alone during the same period were selected as the T2DM group, and 42 healthy individuals on physical examination were the control group. The relative expression of serum miR-20a-5p mRNA was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR); The serum VEGF level was detected by enzyme-linked immunosorbent assay (ELISA); Fasting blood glucose (FBG) was measured by glucose oxidase method and glycosylated hemoglobin (HbA1c) was measured by latex agglutination reaction. The correlation of serum miR-20a-5p with VEGF, FBG, and HbA1c in DR patients was analyzed by Pearson correlation analysis. Multivariate logistic regression was used to analyze the relationship among serum miR-20a-5p, VEGF, and DR. The value of serum miR-20a-5p, VEGF in predicting DR occurrence was analyzed by ROC curve.Results Compared with the control group, the levels of FBG, HbA1c, and VEGF in the DR group significantly increased, while the levels of serum miR-20a-5p significantly decreased in the T2DM group (P < 0.05). Compared with NPDR group, the levels of FBG, HbA1c, and VEGF in PDR group significantly increased, and the level of serum miR-20a-5p significantly decreased (P < 0.05). The serum miR-20a-5p level in DR patients was negatively correlated with FBG, HbA1c, and VEGF levels, while the VEGF level was positively correlated with FBG and HbA1c levels (r = -0611, -0.799 and -0.545, all P < 0.05). Multivariate Logistics regression analysis showed that high serum miR-20a-5p level [O^R = 0.254 (95%CI: 0.154, 0.596)] was an independent protective factor for DR. Duration of diabetes [O^R = 2.042 (95% CI: 1.422, 2.933)], HbA1c [O^R = 2.307 (95% CI: 1.101, 4.833)], and high serum VEGF level [O^R = 2.570 (95% CI: 1.584, 4.144)] were independent risk factors for DR (P < 0.05). ROC curve showed that the sensitivity and specificity of serum miR-20a-5p in predicting Dr were 97.56% (95% CI: 0.915, 0.997) and 61.54% (95% CI: 0.471, 0.748); The sensitivity and specificity of serum VEGF were 57.32% (95% CI: 0.447, 0.683) and 96.15% (95% CI: 0.868, 0.995); The sensitivity and specificity of combined prediction were 91.46% (95% CI: 0.832, 0.965) and 76.92% (95% CI: 0.632, 0.875).Conclusion The serum miR-20a-5p level significantly decreased in DR patients, which was closely related to the levels of FBG, HbA1c, and VEGF. MiR-20a-5p may mediate the occurrence and development of DR by regulating glucose metabolism and VEGF.