帕金森病患者血清miR-124水平与认知损害、炎症及氧化应激反应的相关性

Correlation of serum miR-124 level with cognitive impairment and inflammatory/ oxidative stress response in patients with Parkinson′s disease

目的 探讨不同认知状态下帕金森病(PD)患者血清miR-124表达差异以及与炎症和氧化应激反应的关系。方法 选取2018年3月至2021年9月在该院治疗的PD患者98例为PD组,根据国际帕金森病和运动障碍协会工作组现行临床诊断标准分组,其中轻微认知障碍(PD-MCI)者33例(PD-MCI亚组),痴呆(PDD)者26例(PDD亚组)。将发生认知障碍的PD患者(包括PD-MCI和PDD患者)纳入PD-CI组,将未发生认知障碍的PD患者纳入PD-NC组(39例)。另纳入同期无任何神经和精神疾病史的志愿者50例为对照组。检测各组血清miR-124水平,分析血清miR-124与PD患者认知损害、临床评估量表评分、炎症和氧化应激反应标志物的关系。结果 PD组血清miR-124水平低于对照组(P<0.05),其中PDD亚组血清miR-124水平低于PD-MCI亚组和PD-NC组(P<0.05)。对于PD组患者,血清miR-124水平与PD统一评定量表Ⅲ(UPDRS-Ⅲ)评分、修正Hoehn&Yahr分级、老年抑郁量表评分以及过氧化物歧化酶、过氧化氢酶、丙二醛、晚期氧化蛋白产物、三磷酸腺苷、二磷酸腺苷、腺苷脱氨酶、髓过氧化物酶、白细胞介素(IL)-1β、IL-6、肿瘤生长因子-α水平有关(P<0.05)。多因素Logistic回归分析结果显示,miR-124是PD-CI发生/进展的独立影响因素(P<0.05)。血清miR-124用于区分PDD、PD-MCI时,曲线下面积(AUC)为0.840(95%CI:0.764~0.916);用于区分PD-CI、PD-NC时,AUC为0.844(95%CI:0.766~0.922)。在多元线性回归模型中,控制教育年限和UPDRS-Ⅲ评分后,血清miR-124水平对整体认知状态的影响有统计学意义(β=0.134,t=1.391,P<0.001)。结论 血清miR-124与PD患者认知损害、炎症和氧化应激反应有关,可能成为PD-CI的有效诊断标志物,并有助于进一步了解PD-CI进展的病理生理学机制。

Objective To investigate the expression difference of serum miR-124 in the patients with Parkinson′s disease(PD) under different cognitive states and its relationship with inflammatory/oxidative stress response.Methods A total of 98 PD patients treated in this hospital from March 2018 to September 2021 were selected as the PD group.According to the current clinical diagnostic criteria of the Working Group of the International Parkinson′s Movement Disorders Association, 33 cases were mild cognitive impairment(PD-MCI subgroup) and 26 cases were dementia(PDD subgroup).The PD patients with cognitive impairment(including PD-MCI and PDD) were included into the PD-CI group, and the patients without cognitive impairment were included into the PD-NC group(39 cases).In addition, 50 volunteers without any history of neurological or psychiatric diseases were included as the control group.Serum miR-124 level in each group was detected.The relationship between serum miR-124 level with the cognitive impairment, clinical assessment scale score and markers of inflammation/oxidative stress in PD patients was analyzed.Results The level of serum miR-124 in the PD group was lower than that in the control group(P<0.05),in which the serum miR-124 level in the PDD subgroup was lower than that in the PD-MCI subgroup and PD-NC group(P<0.05).For the PD group, serum miR-124 level was related with the Unified Parkinson Disease Rating Scale 3.0(UPDRS-Ⅲ) score, modified Hoehn&Yahr stage, Geriatric Depression Scale score, and the levels of superoxide dismutase, catalase, malondialdehyde, advanced oxidation protein product, adenosine triphosphate, adenosine diphosphate, adenosine deaminase, myeloperoxidase, interleukin(IL)-1β,IL-6 and tumor necrosis factor-α(P<0.05).The multivariate Logistic regression analysis showed that miR-124 was an independent influencing factor for the occurrence/progression of PD-CI(P<0.05).When serum miR-124 was used to distinguish PDD from PD-MCI,the area under the curve(AUC) was 0.840(95%CI:0.764-0.916),and when used to distinguish PD-CI from PD-NC,AUC was 0.844(95%CI:0.766-0.922).After controlling for years of education and UPDRS-Ⅲ score in the multivariable linear regression model, the effect of serum miR-124 level on overall cognitive status was statistically significant(β=0.134,t=1.391,P<0.001).Conclusion Serum miR-124 is associated with the cognitive impairment, inflammation and oxidative stress in PD patients, which may become an effective diagnostic marker of PD-CI and contribute to further understand the pathophysiological mechanism of PD-CI progression.