血清Sirt2,3-NT水平与帕金森病患者氧化应激和认知功能障碍的关系及其对认知功能障碍的预测价值

The relationship between serum Sirt2,3-NT levels and oxidative stress and cognitive dysfunction in Parkinson's disease patients and its predictive value analysis

目的 探讨血清沉默信息调节因子2(Sirtuin2,Sirt2)、3-硝基酪氨酸(3-Nitrotyrosine, 3-NT)水平与帕金森病(Parkinson’s disease, PD)患者氧化应激和认知功能障碍的关系及其对认知功能障碍的预测价值。方法 纳入本院2019年6月-2022年6月收治的PD患者102例,取同期体检的健康志愿者45例为对照组,根据PD患者的Hoehn-Yahr(H-Y)分期分成早期组(n=32)、中期组(n=40)、晚期组(n=30);比较4组血清Sirt2,3-NT、超氧化物歧化酶(Superoxide dismutase, SOD)、谷胱甘肽过氧化物酶(Glutathione peroxidase, GSH-PX)、对氧磷脂酶1(Paraoxonase 1,PON1)、丙二醛(Malondialdehyde, MDA)水平;采用Pearson线性相关分析PD患者Sirt2,3-NT水平与氧化应激指标水平的相关性;根据蒙特利尔认知评估量表(Montreal cognitive assessment, MoCA)将患者分成认知功能障碍组、非认知功能障碍组;采用多元Logistic回归模型分析认知功能障碍发生的影响因素;采用受试者工作特征(Receiver operating characteristic, ROC)曲线分析Sirt2,3-NT水平对PD患者认知功能障碍的预测价值。结果 早期、中期、晚期组血清Sirt2,3-NT,MDA水平高于对照组,其中中期、晚期组高于早期组,晚期组高于中期组(P<0.05);早期、中期、晚期组血清SOD,GSH-PX,PON1水平低于对照组,且中期、晚期组低于早期组,晚期组低于中期组(P<0.05);PD患者血清Sirt2,3-NT水平与SOD,GSH-PX,PON1水平呈负相关(r≤-0.328,P<0.05),与MDA水平呈正相关(r≥0.511,P<0.05);多元Logistic回归分析显示,病程越长及血清Sirt2,3-NT,MDA水平增高是患者发生认知功能障碍的危险因素,血清GSH-PX,PON1水平增高是预防认知功能障碍的保护因素(P<0.05);ROC分析显示,血清Sirt2、3-NT两指标水平单独及联合应用时ROC-曲线下面积(Area under the curve, AUC)[0.95置信区间(Confidence interval,CI)]分别为0.719(0.448~0.985)、0.742(0.529~0.952)、0.846(0.763~0.914)。结论 PD患者血清Sirt2,3-NT水平升高,且与氧化应激指标水平存在相关性;Sirt2,3-NT水平升高、氧化应激损伤会增加认知功能障碍的发生风险;Sirt2,3-NT水平可预测PD患者认知功能障碍,且联合预测效能更高。

Objective To investigate the relationship between silent information regulatory factor 2(Sirt2)and 3-nitrotyrosine(3-NT)levels and oxidative stress and cognitive dysfunction in patients with Parkinson's disease(PD)and its predictive value.Methods A total of 102 PD patients admitted to our hospital from June 2019 to June 2022 were included,and 45 healthy volunteers who underwent physical examination during the same period were used as the control group.The PD patients were divided into the early stage group(n=32),intermediate stage group(n=40),and late stage group(n=30)according to the Hoehn-Yahr(H-Y)staging of the PD patients.The four groups were compared in terms of the levels of serum Sirt2,3-NT,superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),paraoxonase 1(PON1),and malondialdehyde(MDA).Pearson linear correlation was used to analyze the correlation between the levels of Sirt2,3-NT and oxidative stress indicators in PD patients.The patients were divided into cognitive dysfunction and non-cognitive dysfunction groups according to the Montreal Cognitive Assessment(MoCA),and multivariate logistic regression models were used to analyze the factors affecting the development of cognitive dysfunction.The predictive value of Sirt2 and 3-NT levels on cognitive dysfunction in PD patients was analyzed using receiver operating characteristic(ROC)curves.Results Serum Sirt2,3-NT and MDA levels were higher in the early,middle and late groups than in the control group,which were higher in the middle and late groups than in the early group,and higher in the late group than in the middle group(P<0.05);serum SOD,GSH-PX and PON1 levels were lower in the early,middle and late groups than in the control group,which were lower in the middle and late groups than in the early group,and lower in the late group than in the middle group(P<0.05);Serum Sirt2 and 3-NT levels in PD patients were negatively correlated with SOD,GSH-PX,and PON1 levels(r≤-0.328,P<0.05),and positively correlated with MDA levels(r≥0.511,P<0.05);multivariate logistic regression analysis showed that the longer duration of the disease and increased levels of serum Sirt2,3-NT,and MDA were risk factors for cognitive dysfunction,and increased levels of serum GSH-PX and PON1 were protective factors against cognitive dysfunction(P<0.05);ROC analysis showed that the area under the curve(AUC)of serum Sirt2 and 3-NT when they were applied individually and in combination was[0.95 Confidence Interval(CI)]were 0.719(0.448~0.985),0.742(0.529~0.952),and 0.846(0.763~0.914),respectively.Conclusion Serum Sirt2 and 3-NT levels were elevated in PD patients and correlated with oxidative stress levels.Elevated Sirt2 and 3-NT levels and oxidative stress damage increased the risk of cognitive dysfunction.Sirt2 and 3-NT levels can predict cognitive dysfunction in patients with PD,and the combined predictive efficacy is higher.