血清金属蛋白酶组织抑制剂3和性别决定区Y框蛋白2在2型糖尿病肾损伤早期诊断中的临床应用

张洪利; 王海成; 李华; 未瑞超; 曾玲

doi:10.3969/j.issn.1671-2390.2024.07.001

血清金属蛋白酶组织抑制剂3和性别决定区Y框蛋白2在2型糖尿病肾损伤早期诊断中的临床应用

Clinical applications of serum tissue inhibitor of matrix metalloproteinase 3 and sex determining region Y box protein 2 for an early diagnosis of renal injury in type 2 diabetes mellitus

摘要

摘要:
目的探究血清金属蛋白酶组织抑制剂3（tissue inhibitors of metalloproteinases 3，TIMP3）和性别决定区Y框蛋白2（transcription factor determining region Y box protein 2，SOX2）对2型糖尿病（type 2 diabetes mellitus，T2DM）肾损伤的早期诊断。
方法选取2022年4月至2023年4月在华北石油管理局总医院就诊的102例T2DM患者为研究对象，根据24 h尿蛋白排泄率（urinary albumin excretion rate，UAER）将T2DM患者分为肾损伤组（n = 40）和无肾损伤组（n = 62），另选取同期在华北石油管理局总医院行体检的健康者50名为对照组。酶联免疫吸附法测定所有受试者血清TIMP3、SOX2水平；比较3组受试者一般资料、糖化血红蛋白（hemoglobin A1c，HbA1c）、UAER、血肌酐（serum creatinine，Scr）、估算肾小球滤过率（estimated glomerular filtration rate，eGFR）、血清TIMP3、SOX2水平；Pearson相关性分析血清TIMP3与SOX2及两者与HbA1c、UAER、Scr、eGFR之间的关系；受试者工作特征曲线（receiver operating characteristic curve，ROC）分析血清TIMP3、SOX2对T2DM患者肾损伤的诊断价值。
结果 T2DM患者血清TIMP3（0.68 ± 0.17）μg/L比（1.35 ± 0.35）μg/L及eGFR（105.99 ± 20.56）mL·min⁻¹·（1.73 m²）⁻¹比（133.15 ± 26.18）mL·min⁻¹·（1.73 m²）⁻¹显著低于对照组（P＜0.05），且肾损伤患者血清TIMP3（0.47 ± 0.11）μg/L比（0.82 ± 0.21）μg/L及eGFR（74.69 ± 10.22）mL·min⁻¹·（1.73 m²）⁻¹比（126.18 ± 27.23）mL·min⁻¹·（1.73 m²）⁻¹显著低于无肾损伤患者（P＜0.05）；血清SOX2（8.91 ± 1.82）kU/L比（5.15 ± 1.31）kU/L及HbA1c（8.80 ± 1.55）%比（5.52 ± 0.83）%、UAER（70.13 ± 18.06）mg/24 h比（13.22 ± 3.61）mg/24 h、Scr（82.14 ± 15.23）µmol/L比（53.19 ± 5.62）µmol/L显著高于对照组（P＜0.05），且肾损伤患者血清SOX2（10.81 ± 2.13）kU/L比（5.15 ± 1.31）kU/L及UAER（156.83 ± 40.29）mg/24 h比（13.22 ± 3.61）mg/24 h、Scr（113.77 ± 13.58）µmol/L比（53.19 ± 5.62）µmol/L显著高于无肾损伤患者（P＜0.05）。Pearson相关性分析结果显示，TIMP3与UAER、Scr、HbA1c呈显著负相关（P＜0.05），与eGFR呈显著正相关（P＜0.05）；SOX2与UAER、Scr、HbA1c呈显著正相关（P＜0.05），与eGFR呈显著负相关（P＜0.05）；血清TIMP3与SOX2呈显著负相关（r =−0.590，P＜0.05）。ROC结果显示，血清TIMP3联合SOX2诊断T2DM患者肾损伤的敏感度和特异度分别为95.0%、85.3%，显著高于TIMP3、SOX2单独测定。
结论 T2DM肾损伤患者血清TIMP3水平显著降低，SOX2水平显著升高，且两者与T2DM患者肾损伤密切相关，可用于T2DM患者肾损伤早期诊断。

Abstract:
Objective To explore the roles of serum tissue inhibitor of matrix metalloproteinase 3（TIMP3） and sex determining region Y box protein 2（SOX2） in an early diagnosis of renal injury in type 2 diabetes mellitus（T2DM）.
Methods From April 2022 to April 2023, 102 T2DM patients visiting General Hospital of North China Petroleum Administration Bureau were recruited as research subjects. Based upon 24 h serum urinary protein excretion rate（UAER）, they were assigned into two groups of renal injury（n = 40） and renal non-injury（n = 62）. Another 50 patients undergoing health examinations at General Hospital of North China Petroleum Administration Bureau were regarded as control group. Enzyme-linked immunosorbent assay（ELISA） was utilized for measuring the serum levels of TIMP3 and SOX2. General profiles, serum levels of TIMP3, SOX2, glycosylated hemoglobin（HbA1c）, UAER, serum creatinine（Scr） and glomerular filtration rate（eGFR） of three groups were compared. Pearson’s correlation was utilized for examining the relationship between serum TIMP3/SOX2 and HbA1c, UAER, Scr and eGFR. Receiver operating characteristic curve（ROC） was applied for examining the diagnostic value of serum TIMP3/SOX2 for renal injury in T2DM patients.
Results The serum levels of TIMP3 （0.68 ± 0.17）μg/L vs （1.35 ± 0.35）μg/L and eGFR （105.99 ± 20.56）mL·min⁻¹·（1.73 m²）⁻¹ vs （133.15 ± 26.18）mL·min⁻¹·（1.73 m²）⁻¹ were obviously lower in T2DM patients than those in control group（P＜0.05）. Serum levels of TIMP3 （0.47 ± 0.11）μg/L vs （0.82 ± 0.21）μg/L and eGFR （74.69 ± 10.22）mL·min⁻¹·（1.73 m²）⁻¹ vs （126.18 ± 27.23）mL·min⁻¹·（1.73 m²）⁻¹ were obviously lower in patients with renal injury than those without（P＜0.05）. Serum levels of SOX2 （8.91 ± 1.82）kU/L vs （5.15 ± 1.31）kU/L, HbA1c（8.80 ± 1.55）% vs （5.52 ± 0.83）%, UAER （70.13 ± 18.06）mg/24 h vs （13.22 ± 3.61）mg/24 h and Scr （82.14 ± 15.23）µmol/L vs （53.19 ± 5.62）µmol/L were obviously higher than those in control group（P＜0.05）. Serum levels of SOX2 （10.81 ± 2.13）kU/L vs （5.15 ± 1.31）kU/L, UAER （156.83 ± 40.29）mg/24 h vs （13.22 ± 3.61）mg/24 h and Scr （113.77 ± 13.58）µmol/L vs （53.19 ± 5.62）µmol/L were obviously higher in patients with renal injury than in patients without（P＜0.05）. Pearson’s correlation analysis revealed that TIMP3 was obviously correlated negatively with HbA1c, UAER and Scr（P＜0.05） and positively with eGFR（P＜0.05）. SOX2 was obviously correlated positively with HbA1c, UAER and Scr（P＜0.05） and negatively with eGFR（P＜0.05）. An obvious negative correlation existed between serum TIMP3 and SOX2（r = −0.590, P＜0.05）. The results of ROC indicated that the sensitivity and specificity of serum TIMP3 plus SOX2 in the diagnosis of renal injury in T2DM patients were 95.0% and 85.3% respectively. Both were obviously higher than those of TIMP3 and SOX2 alone.
Conclusions Serum levels of TIMP3 and SOX2 decline markedly and the two are closely correlated with renal injury in T2DM patients. Both may be used for an early diagnosis of renal injury in T2DM patients.

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