[关键词]
[摘要]
目的:探讨原发性青光眼患者血清中沉默信息调节因子6(Sirt6)、还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NOX2)表达水平及其与病情程度的关系。
方法:本研究为横断面研究,纳入2022年8月至2025年6月我院确诊的原发性青光眼患者(根据视野平均缺损值分为轻中度组和重度组)和健康体检者(对照组)。收集两组参与者临床资料,酶联免疫吸附试验(ELISA)检测血清中Sirt6和NOX2表达水平。分析血清中Sirt6和NOX2表达水平与临床指标相关性; 多因素Logistic回归分析影响病情严重程度的因素; 受试者工作特征(ROC)曲线评估血清中Sirt6和NOX2表达水平诊断效能。
结果:本研究共纳入原发性青光眼患者120例,其中男58例,女62例,平均年龄60.08±8.19岁。对照组100名,其中男46例,女56例,平均年龄60.23±8.67岁。两组参与者性别、年龄比较均无差异(均P>0.05)。原发性青光眼组患者眼压、血清中NOX2表达水平明显高于对照组,Sirt6水平显著低于对照组(均P<0.001)。血清中Sirt6和NOX2表达水平诊断原发性青光眼的AUC分别为0.733、0.770,最佳截断值分别为2.35、4.25 ng/mL; 两者联合诊断的AUC为0.901,效能显著优于单一指标(Z联合-Sirt6=5.317、Z联合-NOX2=4.720,均P<0.001)。重度组原发性青光眼患者血清中Sirt6表达水平低于轻中度组(P<0.05),NOX2表达水平高于轻中度组(P<0.05)。原发性青光眼患者血清中Sirt6表达水平与眼压呈负相关(r=-0.354,P<0.05); 血清中NOX2表达水平与眼压呈正相关(r=0.240,P<0.05)。多因素Logistic回归分析显示,血清中Sirt6表达水平降低(OR=0.229,95%CI:0.090-0.581)、NOX2表达水平升高(OR=2.649,95%CI:1.658-4.232)、眼压升高(OR=1.278,95%CI:1.118-1.462)均是影响原发性青光眼患者病情严重程度的因素。血清中Sirt6和NOX2表达水平是诊断重度原发性青光眼的AUC分别为0.794、0.800,两者联合诊断的AUC为0.916,敏感度为80.00%,特异度为89.33%,联合诊断效能优于单一指标(Z联合-Sirt6=2.627,P=0.009; Z联合-NOX2=2.762,P=0.006)。
结论:原发性青光眼患者血清中Sirt6、NOX2表达水平与疾病严重程度显著相关,二者联合检测对原发性青光眼及其严重程度具有较好的诊断价值。
[Key word]
[Abstract]
AIM:To investigate the expression levels of serum sirtuin 6(Sirt6)and nicotinamide adenine dinucleotide phosphate oxidase 2(NOX2)in patients with primary glaucoma and their correlation with the severity of the disease.
METHODS:This study is a cross-sectional study. Patients diagnosed with primary glaucoma at the hospital from August 2022 to June 2025 were enrolled and divided into mild-to-moderate and severe groups based on the mean deviation of visual field defects, along with healthy individuals as a control group. Clinical data were collected, and serum levels of Sirt6 and NOX2 were measured using enzyme-linked immunosorbent assay(ELISA). Correlations between serum Sirt6 and NOX2 levels and clinical parameters were analyzed. Multivariate Logistic regression was used to identify factors influencing disease severity, and the diagnostic efficacy of serum Sirt6 and NOX2 levels was evaluated using receiver operating characteristic(ROC)curves.
RESULTS:A total of 120 patients with primary glaucoma(58 males, 62 females, mean age 60.08±8.19 y)and 100 controls(46 males, 56 females, mean age 60.23±8.67 y)were enrolled in this study. There were no statistically significant differences in sex or age between the two groups(both P>0.05). The intraocular pressure and serum NOX2 expression level in the primary glaucoma group were significantly higher than those in the control group, while the Sirt6 level was significantly lower than in the control group(all P<0.001). The AUC values of serum Sirt6 and NOX2 in the diagnosis of primary glaucoma were 0.733 and 0.770, respectively, with optimal cutoff values of 2.35 and 4.25 ng/mL, respectively. The AUC of the combined diagnosis of the two was 0.901, and its efficacy was obviously better than that of a single indicator(Zcombination-Sirt6=5.317, Zcombination-NOX2=4.720, P<0.001).The severe group had lower serum Sirt6 expression levels(P<0.05), and higher NOX2 expression levels(P<0.05)than the mild-to-moderate group. Serum Sirt6 expression levels were prominently negatively correlated with mean intraocular pressure(r=-0.354, P<0.05); NOX2 expression levels were prominently positively correlated with mean intraocular pressure(r=0.240, P<0.05). Multivariate Logistic regression analysis showed that a decrease in serum Sirt6 expression levels(OR=0.229, 95%CI: 0.090-0.581), an increase in serum NOX2 expression levels(OR=2.649, 95%CI: 1.658-4.232), an increase in mean intraocular pressure(OR=1.278, 95%CI: 1.118-1.462)which were risk factors for the progression to severe glaucoma. The AUC values of serums Sirt6 and NOX2 expression levels in diagnosing severe primary glaucoma were 0.794 and 0.800, respectively, the AUC, sensitivity, and specificity of the combined diagnosis of the two were 0.916, 80.00%, and 89.33%, respectively, and the combined diagnostic efficacy was better than that of a single indicator(Zcombination-Sirt6=2.627, P=0.009, Zcombination-NOX2=2.762, P=0.006).
CONCLUSION:The decreased serum Sirt6 and increased NOX2 expression levels in patients with primary glaucoma are significantly correlated with disease severity, and the combined detection demonstrates good diagnostic value for primary glaucoma and its severity.
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[基金项目]
河北省医学科学研究课题(No.20231822)