帕金森病患者血清NPASDP-4,MBP水平表达与认知功能障碍及严重程度的诊断价值研究

Study on the Diagnostic Value of Serum NPASDP-4 and MBP Level Expression with Cognitive Dysfunction and Severity in Parkinson’s Disease Patients

目的探讨帕金森病患者血清神经元PAS结构域蛋白4(neuronal Per-Arnt-Sim domain protein 4,NPASDP-4)、髓鞘碱性蛋白(myelin basic protein,MBP)水平表达与认知功能障碍(cognitive impairment,CI)及严重程度的诊断价值研究。方法选取中国人民解放军联勤保障部队第九〇九医院收治的138例帕金森病患者为帕金森病组,同期该院体检中心的健康体检者69例为健康对照组,并根据是否发生CI以及其严重程度进一步将帕金森病组患者分为认知功能正常组(n=55)、轻度CI组(n=51)和痴呆组(n=32)。收集受试者一般资料;ELISA法检测血清NPASDP-4和MBP水平;相关性分析采用Spearman等级相关或Pearson线性相关;诊断价值分析采用ROC曲线;影响因素分析采用多因素Logistic回归。结果与健康对照组比较,帕金森病组血清NPASDP-4(6.75±0.48ng/ml vs2.38±0.31ng/ml),MBP(8.34±0.65μg/L vs 3.54±0.42μg/L)水平升高,差异具有统计学意义(t=68.751,55.761,均P<0.05)。认知功能正常组、轻度CI组、痴呆组H-Y分期比较,差异有统计学意义(χ2=7.788,P<0.05)。UPDRS-Ⅲ评分与认知功能正常组(41.95±10.36分)比较,轻度CI组(47.92±11.63分)、痴呆组(50.78±13.69分)评分升高,差异具有统计学意义(H=6.672,均P<0.05)。认知功能正常组、轻度CI组、痴呆组病程(4.28±0.54,4.71±0.58和5.16±0.63年)及血清NPASDP-4(5.89±0.40,6.83±0.55和8.12±0.54ng/ml),MBP(6.65±0.56,8.94±0.69和10.27±0.70μg/L)水平依次显著升高(H=24.114,207.950,355.594,均P<0.05),MMSE评分(28.47±0.94,24.51±1.35和17.09±2.57分)、MoCA评分(27.45±1.03,20.18±1.92和11.75±2.53分)、GPCOG总分(13.47±0.69,10.25±1.04和8.97±0.82分)依次显著降低(H=515.005,775.933,327.584,均P<0.05),差异具有统计学意义。帕金森病患者血清NPASDP-4,MBP水平均与病程(r=0.316,0.358)、H-Y分期(r=0.345,0.384)、UPDRS-Ⅲ评分(r=0.371,0.396)呈显著正相关(P<0.05),与MMSE评分(r=-0.468,-0.517)、MoCA评分(r=-0.504,-0.569)、GPCOG总分(r=-0.527,-0.538)呈显著负相关(均P<0.05)。血清NPASDP-4,MBP水平及二者联合诊断帕金森病患者CI的曲线下面积(AUC)分别为0.850,0.930和0.960,诊断帕金森病患者CI严重程度的AUC分别为0.866,0.803和0.933。H-Y分期中期[OR(95%CI):4.725(1.742~12.814)],H-Y分期晚期[OR(95%CI):5.083(1.919~13.464)]、UPDRS-Ⅲ评分[OR(95%CI):3.257(1.464~7.246)]、NPASDP-4[OR(95%CI):5.324(1.516~18.701)]和MBP[OR(95%CI):5.769(2.459~13.533)]是帕金森病患者CI的影响因素(均P<0.05);NPASDP-4[OR(95%CI):4.768(2.382~9.543)],MBP[OR(95%CI):5.846(3.141~10.882)]是帕金森病患者CI严重程度的影响因素(均P<0.05)。结论帕金森病患者血清NPASDP-4和MBP呈高水平,且均与CI及其严重程度密切相关,可能具有一定的临床诊断价值。

Objective To explore the diagnostic value of serum neuronal Per-Arnt-Sim domain protein 4(NPASDP-4)and myelin basic protein(MBP)expression in patients with Parkinson’s disease in relation to cognitive impairment(CI)and severity.Methods Selected and 138 Parkinson’s disease patients admitted to the 909th Hospital of the Joint Logistics Support Force of the People’s Liberation Army of China as the Parkinson’s disease group,and 69 healthy people in the physical examination center of the hospital were in the healthy control group.Patients with Parkinson’s disease were divided into normal cognitive function group(n=55),mild CI group(n=51)and dementia group(n=32)according to whether CI occurred and its severity.General data of subjects was collected,the serum levels of NPASDP-4 and MBP were detected by ELISA,correlation analysis was adopted by Spearman rank correlation or Pearson linear correlation,diagnostic value was analyzed by ROC curve,and influencing factors were analyzed by multivariate Logistic regression.Results Compared with the healthy control group,the levels of serum NPASDP-4(6.75±0.48 ng/ml vs 2.38±0.31 ng/ml)and MBP(8.34±0.65μg/L vs 3.54±0.42μg/L)in the Parkinson’s disease group were increased with statistical significance(t=68.751,55.761,all P<0.05).There were significant differences in H-Y stage among the normal cognitive function group,mild CI group and dementia group(χ2=7.788,P<0.05).Compared with the group with normal cognitive function(47.92±11.63 score),the mild CI group(50.78±13.69 score)and the dementia group(41.95±10.36 score)showed an increase in UPDRS-III scores,and the differences were statistically significant(H=6.672,all P<0.05).In normal cognitive function group,mild CI group and dementia group,the course of disease,and serum NPASDP-4(5.89±0.40,6.83±0.55,8.12±0.54 ng/ml)and MBP(6.65±0.56,8.94±0.69,10.27±0.70μg/L)levels were significantly increased(H=207.950,355.594,all P<0.05),while MMSE score(28.47±0.94,24.51±1.35,17.09±2.57 score),MoCA score(27.45±1.03,20.18±1.92,11.75±2.53 score)and GPCOG total score(13.47±0.69,10.25±1.04,8.97±0.82 score)were significantly decreased,and the differences were statistically significant(H=515.005,775.933,327.584,all P<0.05),respectively.The serum levels of NPASDP-4 and MBP in Parkinson’s disease patients were significantly positively correlated with the course of disease(r=0.316,0.358),H-Y stage(r=0.345,0.384)and UPDRS-Ⅲscore(r=0.371,0.396),and significantly negatively correlated with MMSE score(r=-0.468,-0.517),MoCA score(r=-0.504,-0.569)and GPCOG total score(r=-0.527,-0.538)(all P<0.05),respectivey.The areas under the curve(AUC)of the serum levels of NPASDP-4,MBP and their combination in diagnosing of Parkinson’s disease were 0.850,0.930 and 0.960,respectively.The AUC of the serum levels of NPASDP-4 and MBP and their combination in diagnosing the severity of CI in patients with Parkinson’s disease were 0.866,0.803 and 0.933,respectively.H-Y stage metaphase[OR(95%CI):4.725(1.742~12.814)],H-Y stage advanced[OR(95%CI):5.083(1.919~13.464)],UPDRS-Ⅲscore[OR(95%CI):3.257(1.464~7.246)],NPASDP-4[OR(95%CI):5.324(1.516~18.701)]and MBP[OR(95%CI):5.769(2.459~13.533)]were the influential factors for CI in patients with Parkinson’s disease(all P<0.05).NPASDP-4[OR(95%CI):4.768(2.382~9.543)]and MBP[OR(95%CI):5.846(3.141~10.882)]were the influential factors for the severity of CI in patients with Parkinson’s disease(all P<0.05).Conclusion The serum levels of NPASDP-4 and MBP in patients with Parkinson’s disease were high,and they were closely related to CI and its severity,which may have certain clinical diagnostic value.