目的：分析血脑屏障标志物闭合蛋白（Occludin，OCLN）、密封蛋白-5（Claudin-5，CLDN5）与帕金森病（PD）患者神经功能损伤程度及不良预后的关联。方法：研究对象选择2024年6月~2025年6月就诊于我院的180例PD患者，及同期接受检查的180例健康志愿者，将其分别列为病例组、对照组，比较两组OCLN、CLDN5间差异。依据病情严重程度不同，将PD患者分别列为早期组（50例）、中期组（65例）和晚期组（65例），比较三组患者OCLN、CLDN5，神经损伤标志物间差异，分析晚期组患者OCLN、CLDN5与神经损伤标志物的相关性。统计入组患者不良预后发生情况，比较不同预后患者OCLN、CLDN5及神经损伤标志物间差异，分析PD患者预后影响因素，验证OCLN、CLDN5对PD患者不良预后的预测效能。结果：病例组的外周血OCLN、CLDN5均高于对照组（t=50.450，51.670；P＜0.05）。晚期组外周血OCLN、CLDN5、神经元特异性烯醇化酶（NSE）、泛素羧基末端水解酶L1（UCH-L1）、神经丝轻链蛋白（NfL）、胶质纤维酸性蛋白（GFAP）均高于中期组、早期组（F=280.611，378.453，82.254，122.413，185.272，257.733；P＜0.05）。晚期组的OCLN、CLDN5均与NSE、UCH-L1、NfL、GFAP正相关（r=0.411，0.457，0.505，0.494，0.465，0.425，0.491，0.503；P＜0.05）。180例PD患者的不良预后发生率为28.89%（52/180）。预后不良组的外周血OCLN、CLDN5、NSE、UCH-L1、NfL、GFAP均高于预后良好组（t=17.096，14.405，7.632，6.903，11.695，10.702；P＜0.05）。Logistic多因素回归分析结果显示，外周血OCLN、CLDN5、NfL、GFAP高表达为PD患者发生不良预后的危险因素。经ROC检验，外周血OCLN、CLDN5联合检测对于PD不良预后的预测AUC高于外周血OCLN、CLDN5单独检测（DeLong检验，P＜0.05）。结论：外周血OCLN、CLDN5可随PD患者神经损伤程度加剧而不断升高，联合检测外周血OCLN、CLDN5或可作为预测患者不良预后的重要辅助手段。
Objective:To analysis of the association between blood-brain barrier markers Occludin (OCLN), Claudin-5 (CLDN5) and the degree of neurological damage and poor prognosis in PD patients.Methods:The research subjects selected 180 PD patients who visited our hospital from June 2024 to June 2025, as well as 180 healthy volunteers who underwent examinations during the same period. They were divided into a case group and a control group, and the differences between the two groups in terms of OPLN and CLDN5 were compared. According to the severity of the disease, PD patients were divided into early group (50 cases), middle group (65 cases), and late group (65 cases). The differences in OCLN, CLDN5, and nerve injury markers among the three groups of patients were compared, and the correlation between OCLN, CLDN5, and nerve injury markers in the late group of patients was analyzed. Statistically analyze the occurrence of poor prognosis in enrolled patients, compare the differences in OCLN, CLDN5, and nerve injury markers among patients with different prognoses, analyze the factors affecting the prognosis of PD patients, and verify the predictive power of OCLN and CLDN5 for poor prognosis in PD patients.Results:The peripheral blood levels of OCLN and CLDN5 in the case group were higher than the control group (t=50.450，51.670; P<0.05). The levels of OCLN, CLDN5 NSE,UCH-L1,NfL, and GFAP in peripheral blood of the late stage group were higher than those of the mid stage and early stage groups (F=280.611，378.453，82.254，122.413，185.272，257.733; P<0.05). The OCLN and CLDN5 in the late stage group were positively correlated with NSE, UCH-L1, NfL, and GFAP (r=0.411，0.457，0.505，0.494，0.465，0.425，0.491，0.503; P<0.05). The incidence of poor prognosis in 180 PD patients was 28.89% (52/180). The peripheral blood levels of OCLN, CLDN5, NSE, UCH-L1, NfL, and GFAP in the poor prognosis group were higher than those in the good prognosis group (t=17.096，14.405，7.632，6.903，11.695，10.702; P<0.05). The results of logistic multiple regression analysis showed that high expression of peripheral blood OCLN, CLDN5, NfL, and GFAP were risk factors for poor prognosis in PD patients. According to ROC test, the combined detection of peripheral blood OCLN and CLDN5 has a higher AUC for predicting poor prognosis of PD than the detection of peripheral blood OCLN and CLDN5 alone (DeLong test, P<0.05).Conclusion:Peripheral blood OCLN and CLDN5 can exacerbate and continuously increase the degree of nerve damage in PD patients. Combined detection of peripheral blood OCLN and CLDN5 may serve as an important auxiliary tool for predicting poor prognosis in patients.
