早发型子痫前期患者血清mTOR、Nrf2表达水平变化及其与病情严重程度的相关性研究

Study on the changes in serum mTOR and Nrf2 expression levels in patients with early-onset preeclampsia and their correlation with disease severity

摘要

目的 分析早发型子痫前期患者的血清雷帕霉素靶蛋白(mTOR)、核因子红细胞2相关因子2(Nrf2)表达水平变化及其与病情严重程度的相关性.方法 选取2020年12月至2022年12月在本院收治的早发型子痫前期患者共200例作为研究对象,根据患者病情程度分为轻度组(n=109)和重度组(n=91),另选同期进行孕检的健康孕妇作为对照组(n=88).采用ELISA检测患者血清mTOR、Nrf2的表达水平,并收集患者的一般资料.使用Pearson相关分析mTOR、Nrf2与临床指标的相关性;采用Spearman相关分析mTOR、Nrf2与病情程度的相关性;使用Logistic回归分析影响患者病情程度的因素;绘制受试者工作特征(ROC)曲线分析血清mTOR、Nrf2对患者病情程度诊断价值.结果 与对照组相比,病例组血清mTOR表达水平显著升高,Nrf2水平显著降低(t=9.071、10.645,P<0.05);与轻度组相比,重度组血清mTOR表达水平显著升高,Nrf2水平显著降低(t=8.237、9.007,P<0.05);重度组新生儿体重显著低于轻度组(t=3.143,P<0.05);重度组收缩压、舒张压、24h尿蛋白定量、肌酐、尿素氮、尿酸、低密度脂蛋白、甘油三脂以及总胆固醇均显著高于轻度组(t值介于2.432~30.838之间,P<0.05);mTOR与收缩压、舒张压、24h尿蛋白定量、肌酐、尿素氮、尿酸、低密度脂蛋白、甘油三酯、总胆固醇以及病情程度呈正相关(r值介于0.403~0.518之间,P<0.05),Nrf2与上述临床指标、病情程度呈负相关(r值介于-0.404~-0.537之间,P<0.05);收缩压、舒张压、24h尿蛋白定量、低密度脂蛋白以及mTOR均为影响患者病情严重程度的危险因素,OR值及其95%置信区间分别为1.368(1.058~1.768)、1.477(1.092~1.997)、1.854(1.116~3.080)、1.674(1.064~2.633)、1.743(1.098~2.768),Nrf2为影响患者病情严重程度的保护因素,OR值及其95%置信区间为0.742(0.573~0.961);血清mTOR、Nrf2以及两者联合诊断患者病情程度的AUC分别为0.759(0.694~0.817)、0.809(0.747~0.861)、0.863(0.808~0.908),联合诊断显著优于mTOR(Z=3.334,P=0.001)、Nrf2(Z=2.199,P=0.028)单独诊断.结论 早发型子痫前期患者血清mTOR水平升高,Nrf2水平降低,两者与患者病情程度具有相关性,对患者病情程度的评估具有一定参考价值.

Abstract

Objective To analyze the changes in serum expression levels of target protein of rapamycin (mTOR) and nuclear factor erythrocyte 2-related factor 2 (Nrf2) in patients with early-onset preeclampsia and their correlation with disease severity. Methods A total of 200 patients with early-onset preeclampsia admitted to our hospital from December 2020 to December 2022 were selected as the study subjects, and they were divided into mild group (n=109) and severe group (n=91) according to the severity of the disease, and healthy pregnant women who underwent pregnancy testing at the same time were selected as the control group (n=88). ELISA was used to detect the expression levels of serum mTOR and Nrf2, and the general data of the patients were collected and analyzed. Pearson correlation was used to analyze the correlation between mTOR and Nrf2 and clinical indicators. Spearman correlation analysis was used to analyze the correlation between mTOR and Nrf2 and disease severity. Logistic regression was used to analyze the factors affecting the severity of the patient's disease. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic value of serum mTOR and Nrf2 on the severity of the patient's condition. Results Compared with the control group, the serum mTOR expression level and Nrf2 level in the case group were significantly increased (t=9.071, 10.645, respectively, P<0.05), compared with the mild group, the serum mTOR expression level in the severe group was significantly increased, and the Nrf2 level was significantly decreased (t=8.237, 9.007, respectively, P<0.05), and the neonatal body weight in the severe group was significantly lower than that in the mild group (t=3.143, P<0.05). The 24-hour urine protein quantification, creatinine, urea nitrogen, uric acid, low-density lipoprotein, triglycerides and total cholesterol were significantly higher than those in the mild group (t-values ranged from 2.432 to 30.838, P<0.05), and mTOR was positively correlated with systolic blood pressure, diastolic blood pressure, 24-hour urine protein quantification, creatinine, urea nitrogen, uric acid, low-density lipoprotein, triglycerides, total cholesterol and disease severity (r values ranged from 0.403 to 0.518, P<0.05), Nrf2 was negatively correlated with the above clinical indicators and severity of disease (r values ranged from -0.404 to -0.537, P<0.05). Systolic blood pressure, diastolic blood pressure, 24-hour urine protein quantification, low-density lipoprotein and mTOR were all risk factors affecting the severity of the disease, and the OR and its 95% CI were 1.368 (1.058-1.768), 1.477 (1.092-1.997), 1.854 (1.116-3.080), 1.674 (1.064-2.633), and 1.743 (1.098-2.768), respectively. Nrf2 was a protective factor affecting the severity of the patient's disease, and the OR and its 95% CI were 0.742 (0.573-0.961). The AUC of serum mTOR, Nrf2 and the combined diagnosis of disease severity were 0.759 (0.694-0.817), 0.809 (0.747-0.861) and 0.863 (0.808-0.908), respectively, which were significantly better than those of mTOR (Z=3.334, P=0.001) and Nrf2 (Z=2.199, P=0.028). Conclusion The increase in serum mTOR level and the decrease in Nrf2 level in patients with early-onset preeclampsia are correlated with the severity of the patient's disease, which has certain reference value for the evaluation of the patient's disease.

关键词

早发型子痫前期 / 雷帕霉素靶蛋白 / 核因子红细胞2相关因子2 / 病情程度

Key words

early onset preeclampsia / mammalian target of rapamycin / nuclear factor-erythroid 2 related factor 2 / severity of condition

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基金资助

河北省2022年度医学科学研究课题(20220553)