帕金森病患者血清Sirtuin1、SGK1水平与病情分期及认知障碍的关系-东南大学学报医学版

帕金森病患者血清Sirtuin1、SGK1水平与病情分期及认知障碍的关系

单位：1. 河北北方学院附属第二医院检验科, 河北张家口 075100;
2. 河北北方学院附属第二医院神经内科, 河北张家口 075100

关键词：帕金森病沉默信息调节蛋白1 血清和糖皮质激素调节激酶1 病情分期认知障碍

分类号：R749.16

出版年·卷·期（页码）：2025·44·第四期（586-592）

摘要：

目的:探讨帕金森病(PD)患者血清沉默信息调节蛋白1(Sirtuin1)、血清和糖皮质激素调节激酶1(SGK1)水平变化与疾病分期及认知障碍的相关性。方法:选取本院神经内科2021年7月至2022年12月诊治的116例PD患者(PD组),根据不同认知障碍程度,分为认知障碍组(n=68例)和认知正常组(n=48例);根据PD分期,分为早期PD组(45例)、中期PD组(40例)和晚期PD组(31例)。同期选取86例健康志愿者作为对照组。ELISA法检测Sirtuin1、SGK1水平;采用Spearman和Pearson法分析其相关性;Logistic回归分析影响因素,并使用Logistic回归分析构建联合检测模型进行受试者工作特征(ROC)曲线分析。结果:PD组患者SGK1水平高于对照组[(1.70±0.77) mg·L^-1 vs.(1.13±0.38) mg·L^-1],受教育程度、Sirtuin1水平低于对照组[(7.49±1.32)年 vs.(10.06±2.08)年、(0.91±0.21) mg·L^-1 vs.(1.22±0.37) mg·L^-1],差异有统计学意义(均P＜0.05)。血清Sirtuin1水平随PD严重程度的增加而降低,SGK1水平升高,差异有统计学意义(t值分别为5.270、17.805,均P<0.05);相较于认知正常组,认知障碍组患者MoCA评分和血清Sirtuin1水平显著降低(t值分别为7.346、6.158,均P<0.05),血清SGK1水平显著升高(t=7.576,P<0.05)。PD患者血清Sirtuin1与H-Y分期呈负相关(r=-0.487,P<0.05),与MoCA评分、MMSE评分呈正相关(r值分别为0.465、0.537,均P<0.05);血清SGK1与H-Y分期呈正相关(r=0.511,P<0.05),与MoCA评分、MMSE评分呈负相关(r值分别为-0.561、-0.518,均P<0.05);血清Sirtuin1与SGK1呈负相关(r=-0.556,P<0.05)。Logistic回归分析表明,PD患者受教育程度高、血清Sirtuin1水平升高为PD发生认知功能障碍的保护因素[OR(95%CI)分别为0.744(0.587~0.943)、0.512(0.345~0.759)],PD患者血清SGK1水平升高是PD发生认知障碍的危险因素[OR(95%CI)=2.503(1.454~4.308)];血清Sirtuin1、SGK1诊断PD发生认知障碍患者的AUC分别为0.800、0.857,联合诊断的AUC为0.928,两者联合优于各自单独诊断(Z_{两者联合-}_Sirtuin1=3.500,Z_{两者联合-SGK1}=2.139,均P<0.05)。结论:PD患者血清Sirtuin1水平降低、SGK1水平升高,且两者均与患者的病情分期、认知障碍存在相关性,临床上可将血清Sirtuin1、SGK1水平作为评估PD病情进展的指标。

Objective: To investigate the correlation between changes in serum Sirtuin1 and SGK1 levels with disease staging and cognitive impairment in patients with Parkinson's disease(PD). Methods: A total of 116 PD patients diagnosed and treated in the neurology department of our hospital from July 2021 to December 2022 were included as the PD group. According to the degree of cognitive impairment, they were divided into a cognitive impairment group(n=68) and a cognitive normal group(n=48). According to PD staging, the group was divided into early PD group(n=45), middle PD group(n=40) and late PD group(n=31). ELISA method was applied to measure the levels of Sirtuin1 and SGK1. Correlations were analyzed using the Spearman and Pearson method. Logistic regression was used to analyze the influencing factors. And use Logistic regression analysis was used to construct a joint detection model for ROC curve analysis. Results: SGK1 level of the PD group were higher than those of the control group[(1.70±0.77) mg·L^-1 vs.(1.13±0.38) mg·L^-1], while the levels of education and Sirtuin1 level of the PD group was lower than that of the control group[(7.49±1.32) years vs.(10.06±2.08) years,(0.91±0.21) mg·L^-1 vs.(1.22±0.37) mg·L^-1], and the differences were statistically significant(all P<0.05). The serum Sirtuin1 level decreased with the increase of PD severity, while the SGK1 level increased, and the difference was statistically significant(t=5.270, 17.8051, all P<0.05). Compared to the cognitively normal group, patients in the cognitively impaired group had significantly lower MoCA scores and serum Sirtuin1 levels(t=7.346, 6.158, all P<0.05) and significantly higher serum SGK1 levels(t=7.576, P<0.05). In PD patients, serum Sirtuin1 was negatively correlated with H-Y staging(r=-0.487, P<0.05) and positively correlated with MoCA scores and MMSE scores(r=0.465, 0.537, all P<0.05), serum SGK1 was positively correlated with H-Y staging(r=0.511, P<0.05), and was negatively correlated with MoCA scores and MMSE scores(r=-0.561,-0.518, all P<0.05), serum Sirtuin1 was negatively correlated with SGK1(r=-0.556, P<0.05). Logistic regression analysis reveled that high educational attainment, elevated serum Sirtuin1 level in PD patients were protective factors for the development of cognitive dysfunction in PD [OR(95% CI)=0.744(0.587-0.943),0.512(0.345-0.759)], and elevated serum SGK1 level in PD patients was a risk factor for the development of cognitive impairment in PD [OR(95% CI)=2.503(1.454-4.308)]. The AUCs of serum Sirtuin1 and SGK1 for diagnosing patients occurring cognitive impairment in PD were 0.800 and 0.857, respectively, and the AUC for the combined diagnosis was 0.928, and the combination of the two was superior to their respective individual diagnoses(Z_{combination-Sirtuin1}=3.500, Z_{combination-SGK1}=2.139, P<0.05). Conclusion: Serum Sirtuin1 level is reduced and SGK1 level is increased in PD patients, and both are correlated with the disease staging and cognitive impairment. Clinically, serum Sirtuin1 and SGK1 levels can be used as indicators to evaluate the progression of PD.

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