Values of serum Delta-like protein 4 and cAMP response element-binding protein levels in predicting microvascular injury of patients with different stages of diabetic retinopathy
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摘要:目的
分析糖尿病视网膜病变（DR）不同分期患者血清δ样蛋白4（DLL4）和环磷腺苷效应元件结合蛋白（CREB）水平对微血管损伤的预测价值。
方法选择2020年2月—2023年2月收治的80例糖尿病患者为研究对象，依据DR不同分期分为无DR组（n=37）、非增生型DR组（n=19）和增生型DR组（n=24）；检测血中DLL4及CREB水平，采用FACS Count流式细胞仪检测患者内皮祖细胞（EPC）、循环内皮细胞（CEC）及循环祖细胞（CPC）水平。
结果增生型DR组血中DLL4及CREB水平最高，无DR组DLL4及CREB水平最低，差异有统计学意义（P＜0.05）；不同DR分期与DLL4、CREB水平呈显著正相关（P＜0.05）；糖尿病患者血中高DLL4及高CREB水平是影响DR分期的独立危险因素（P＜0.05）。增生型DR组血中EPC、CPC水平最低，CEC水平最高，无DR组EPC、CPC水平最高，CEC水平最低，差异均有统计学意义（P＜0.05）；DLL4、CREB水平与EPC、CPC水平呈显著负相关（P＜0.05），DLL4、CREB水平与CEC水平呈显著正相关（P＜0.05）；DLL4和CREB预测DR患者微血管损伤的曲线下面积（AUC）均大于0.85。
结论随着DR分期增加，患者血清DLL4和CREB水平呈显著升高趋势，且DLL4和CREB对其微血管损伤具有较高的预测价值。
Abstract:ObjectiveTo analyze the values of serum Delta-like protein 4 (DLL4) and cAMP response element-binding protein (CREB) levels in predicting microvascular injury of patients with different stages of diabetic retinopathy (DR).
MethodsEighty diabetic patients from February 2020 to February 2023 were selected as research objects, and they were divided into no DR group (n=37), non-proliferative DR group (n=19) and proliferative DR group (n=24) according to different stages of DR; serum DLL4 and CREB levels in the blood were detected, and the FACS Count flow cytometry was used to detect levels of endothelial progenitor cells (EPC), circulating endothelial cells (CEC) and circulating progenitor cells (CPC) in patients.
ResultsThe levels of DLL4 and CREB in the blood of proliferative DR group were the highest, while the levels of DLL4 and CREB in the no DR group were the lowest, and the differences were statistically significant (P < 0.05); different stages of DR were significantly positively correlated with the levels of DLL4 and CREB (P < 0.05); the high levels of DLL4 and CREB in the blood of diabetic patients were the independent risk factors affecting staging of DR (P < 0.05). The levels of EPC and CPC in the blood of proliferative DR group were the lowest, while the level of CEC was the highest; in the no DR group, the levels of EPC and CPC were the highest, while the level of CEC was the lowest, and the differences were statistically significant (P < 0.05); the levels of DLL4 and CREB were significantly negatively correlated with EPC and CPC levels (P < 0.05), while the levels of DLL4 and CREB were significantly positively correlated with CEC level (P < 0.05); the area under the curve (AUC) of both DLL4 and CREB in predicting microvascular injury in DR patients was greater than 0.85.
ConclusionAs the staging of DR increases, the levels of serum DLL4 and CREB show a significant upward trend, and DLL4 and CREB have higher predictive values for microvascular injury.
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表 1 3组患者血中DLL4及CREB水平比较(x±s)
pg/mL 组别 n DLL4 CREB 无DR组 37 50.13±7.58 0.67±0.10 非增生型DR组 19 66.29±12.11 0.82±0.09 增生型DR组 24 77.31±11.94 0.98±0.12 F 6.121 5.968 P 0.003 0.004 DLL4: δ样蛋白4; CREB: 环磷腺苷效应元件结合蛋白。 
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表 2 DLL4和CREB水平对DR患者分期的影响
指标 b SE χ2 P OR 95%CI 下限 上限 DLL4 0.647 0.192 11.355 0.001 1.910 1.311 2.782 CREB 0.712 0.201 12.548 ＜0.001 2.038 1.374 3.022
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表 3 3组患者微血管损伤指标比较(x±s)
% 组别 n EPC CEC CPC 无DR组 37 0.067±0.013 0.072±0.009 0.178±0.023 非增生型DR组 19 0.057±0.009 0.095±0.010 0.135±0.031 增生型DR组 24 0.038±0.010 0.138±0.012 0.085±0.028 F 6.144 5.986 5.685 P 0.003 0.004 0.005 EPC: 内皮祖细胞; CEC: 循环内皮细胞; CPC: 循环祖细胞。
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表 4 DLL4和CREB水平与微血管评估指标的相关性
指标 模型 R2 EPC对比DLL4 y=-0.001 0x+0.115 6 0.908 2 CEC对比DLL4 y=0.001 7x-0.008 2 0.979 8 CPC对比DLL4 y=-0.002 4x+0.295 1 0.984 0 EPC对比CREB y=-0.105 0x+0.138 5 0.934 5 CEC对比CREB y=0.185 0x-0.050 6 0.954 0 CPC对比CREB y=-0.961 9x+0.282 1 0.925 2
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表 5 DLL4和CREB对微血管损伤的预测价值
指标 AUC SE P 95%CI 下限 上限 DLL4 0.898 0.042 ＜0.001 0.816 0.980 CREB 0.854 0.051 ＜0.001 0.754 0.954
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