血浆CXCL12对帕金森病及帕金森病患者发生认知功能障碍的预测价值

Value of plasma CXCL12 to the prediction of Parkinson's disease and cognitive impairment in Parkinson's disease patients

目的 观察帕金森病(Parkinson’s disease, PD)患者血浆CXCL12水平变化,探讨其诊断PD及预测PD患者发生认知功能障碍的价值。方法 PD患者105例为PD组,同期体检健康者106例为对照组。PD患者于入院次日、对照组于体检日清晨采集空腹静脉血,采用ELISA法测定血浆CXCL12水平。PD患者入院后采用帕金森病评定量表评分(unified Parkinson’s disease rating scale, UPDRS)评估PD严重程度,采用简易智能精神状态检查量表(mini-mental state examination, MMSE)评估认知功能,并进行分组。UPDRS评分<62分53例为轻度组,≥62分52例为重度组。MMSE评分11~23分29例为认知功能障碍组,24~30分76例为无认知功能障碍组。比较PD组与对照组、轻度组与重度组、认知功能障碍组与无认知功能障碍组血浆CXCL12水平;Pearson相关法分析PD患者血浆CXCL12水平与PD病程、UPDRS评分、MMSE评分的相关性;绘制ROC曲线,评估血浆CXCL12诊断PD、预测PD患者发生认知功能障碍的效能。结果 (1)PD组血浆CXCL12水平[(539.08±164.45)ng/L]高于对照组[(408.13±130.47)ng/L](t=-6.404,P<0.001),年龄、男性及合并高血压、糖尿病比率与对照组比较差异均无统计学意义(P>0.05)。(2)血浆CXCL12水平在重度组[(573.75±163.35)ng/L]高于轻度组[(505.06±159.80)ng/L](t=-2.178,P=0.032),在认知功能障碍组[(603.42±127.22)ng/L]高于无认知功能障碍组[(514.53±171.01)ng/L](t=-2.541,P=0.013)。(3)PD患者血浆CXCL12水平与PD病程、UPDRS评分均呈正相关(r=0.293,P=0.002;r=0.213,P=0.029),与MMSE评分呈负相关(r=-0.240,P=0.014)。(4)血浆CXCL12以515.71 ng/L为最佳截断值,诊断PD的AUC为0.733(95%CI:0.666~0.800,P<0.001),灵敏度为82.1%,特异度为58.1%;以544.64 ng/L为最佳截断值,预测PD患者发生认知功能障碍的AUC为0.682(95%CI:0.573~0.792,P=0.004),灵敏度为60.5%,特异度为72.4%。结论 PD患者血浆CXCL12水平增高,且增高程度与病程、病情严重程度和发生认知功能障碍有关,血浆CXCL12对PD和PD患者发生认知功能障碍具有一定的诊断价值。

Objective To observe the change of plasma CXCL12 level in patients with Parkinson's disease(PD),and to explore its values to the diagnosis of PD and prediction of cognitive impairment.Methods The fasting venous blood was obtained to detect the plasma CXCL12 level by ELISA the next day after admission in 105 PD patients(PD group)and on the day of physical examination in 106 healthy volunteers(control group).Unified Parkinson's disease rating scale(UPDRS)was done to evaluate the severity of PD,and mini-mental state examination(MMSE)was done to assess the cognitive function of PD patients.PD group was divided into 53 patients with UPDRS score 62(mild group)and 52 patients with UPDRS score≥62(severe group),and 29 patients with MMSE score of 11 to 23(cognitive impairment group)and 76 patients with MMSE score of 24 to 30(non-cognitive impairment group).The plasma CXCL12 levels were compared between PD group and control group,between mild group and severe group,and between cognitive impairment group and non-cognitive impairment group.Spearman correlation analysis was used to assess the correlations of plasma CXCL12 level with the disease course,UPDRS score and MMSE score.ROC curves were plotted to evaluate the efficiency of plasma CXCL12 on the diagnosis of PD and prediction of cognitive impairment in PD patients.Results(1)The plasma CXCL12level was higher in PD group[(539.08±164.45)ng/L]than that in control group[(408.13±130.47)ng/L](t=-6.404,P<0.001),and there were no significant differences in the age,male ratio and the percentages of patients with hypertension and diabetes between two groups(P>0.05).(2)The plasma CXCL12level was higher in severe group[(573.75±163.35)ng/L]than that in mild group[(505.06±159.80)ng/L](t=-2.178,P=0.032),and higher in cognitive impairment group[(603.42±127.22)ng/L]than that in non-cognitive impairment group[(514.53±171.01)ng/L](t=-2.541,P=0.013).(3)The plasma CXCL12level in PD patients was positively correlated with PD disease course and UPDRS score(r=0.293,P=0.002;r=0.213,P=0.029),and negatively correlated with MMSE score(r=-0.240,P=0.014).(4)When the optimal cut-off value of plasma CXCL12was515.71ng/L,the AUCfor diagnosing PD was 0.733(95%CI:0.666-0.800,P<0.001),with a sensitivity of 82.1%,and a specificity of 58.1%.When the optimal cut-off value of plasma CXCL12 was 544.64ng/L,the AUCfor diagnosing cognitive impairment in PD patients was 0.682(95%CI:0.573-0.792,P=0.004),with a sensitivity of60.5%and a specificity of 72.4%.Conclusion The plasma CXCL12level increases in PD patients,which is correlated with the disease course,the severity of PD and the occurrence of cognitive impairment,and the plasma CXCL12has a certain value to the diagnosis of PD and prediction of cognitive impairment in PD patients.