迟发性阿尔茨海默病患者血清尿激酶型纤溶酶原激活因子浓度的测定及其意义

Determination and significance of the concentration of urokinase-type plasminogen activator in serum in late-onset Alzheimer's disease

目的探讨血清尿激酶型纤溶酶原激活因子(urokinase-type plasminogen activator,uPA)浓度与迟发型阿尔茨海默病(late-onset Alzheimer's disease,LOAD)的关系。方法采用酶联免疫吸附法测定55例LOAD患者和61例正常对照者外周血清uPA的浓度,并通过聚合酶链反应限制性片段长度多态性方法对所有病例进行plau基因P141L多态性基因分型,进一步对不同基因型的uPA浓度进行分层分析。结果病例组与对照组,血清uPA浓度差异无统计学意义(P>0.05),轻度、中-重度LOAD组及对照组3组血清uPA的浓度比较差异也无统计学意义(P>0.05);基因型C/C组与C/T组血清uPA浓度显著高于T/T组,差异均有统计学意义(P<0.01)。结论 LOAD患者外周血清uPA的浓度不能作为AD诊断的标志物,也不能反映患者痴呆的程度;plau基因第6外显子上的错义C→T突变可减少血清uPA的浓度,对探讨AD的发病机制提供新思路。

Objective To study the association between the levels of urokinase-type plasminogen activator（uPA） in serum and late-onset Alzheimer’s disease（LOAD）.Methods ELISA was adopted to determine the concentration of uPA in serum of the 44 LOAD sufferers and 40 subjects from the control group.The polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） technique was used in detecting the polymorphism of the P141L polymorphisms of urokinase plasminogen activator gene（PLAU） in all cases,and to analyze the concentration of the uPA of different genotypes.Results The difference in the concentration of uPA in blood serum between the LOAD group and the control group was not significant（P〉0.05）,either was the difference among the singulorum degree of LOAD groups and the control group（P〉0.05）.The concentration of uPA in C/C genotype group and C/T genotype group were both higher than T/T genotype group,and the difference among the three groups was significant statistically（P〈0.01）.Conclusion The uPA level of LOAD sufferers in serum cannot be taken as the biomarker for the diagnosis of AD.Neither can it reflect the degrees of dementia.The concentration of uPA in T/T genotype group is lower than that in C/T and C/C group,indicating that the C→T mutation in exons 6 of PLAU gene may reduce the level of uPA,which might provide a new ideas to research on pathogenesis of AD.