摘要
目的通过对阿尔茨海默病(Alzheimer’s disease,AD)和血管性痴呆(vascular dementia,VD)患者血液中高分子量激肽原重链蛋白(heavy chain of high molecular-weight kininogen,hc-HK)和激肽释放酶-6(kallikrein-6,KLK-6)的比较分析,从神经性炎症反应信号通路角度探索AD的发病机制。方法收集AD组、VD组和对照组各15例的外周血标本,分别用蛋白质免疫印迹法检测其中hc-HK蛋白含量,用酶联免疫吸附法检测其中Aβ42和KLK-6蛋白的含量;并对Aβ42与KLK-6进行相关性分析。结果 AD患者外周血中hc-HK含量较VD组或对照组均显著增加(均P<0.01)。AD组患者血液中的KLK-6水平为(4.80±0.78)ng/mL,VD组KLK-6为(3.72±0.87)ng/mL,AD组较VD组明显增加(t=3.57,P<0.01)。AD组患者血浆中Aβ42蛋白浓度为(0.261±0.024)μg/L,与VD组或对照组比较均明显增加(均P<0.01)。通过相关分析发现,在AD组患者血液中KLK-6与Aβ42的增加呈正相关(r=0.65,P<0.01)。结论AD患者外周血液中hc-HK和KLK-6蛋白比VD患者及非痴呆对照有明显增加,提示AD发病中有血凝接触系统的激活;激肽释放酶-激肽系统的异常激活有可能参与了AD的发病过程。
Objective To explore the involvement of neurogenic inflammatory pathway in Alzheimer’s disease(AD)by examining the levels of the heavy chain of high molecular-weight kininogen(hc-HK)and kallikrein-6(KLK-6)in the blood of patients with AD and with vascular dementia(VD).Methods The blood samples were collected from patients in AD,VD and control groups(n=15 each).The hc-HK protein levels were detected by Western blotting and the activities of Aβ42 and KLK-6 by enzyme-linked immunosorbent assay(ELISA).Univariate correlation analysis was performed between Aβ42 and KLK-6. Results The level of hc-HK was significantly increased in AD group as compared with VD and control groups(both P<0.01).The level of KLK-6 was(4.80±0.78)ng/mL in AD group,significantly higher than(3.72±0.87)ng/mL in VD group(t=3.57,P<0.01).The concentration of Aβ42 protein was(0.261±0.024)μg/L in AD group,which was markedly enhanced as compared with that in VD and control groups.In addition,the univariate regression analysis showed that KLK-6 was positively correlated with Aβ42 in patients with AD(r=0.65,P<0.01).Conclusion hc-HK and KLK-6 protein significantly increase in the peripheral blood of AD patients,which supports the activation of the coagulation contact system in AD and the involvement of the abnormal activation of the kallikrein-kinin system in the pathogenesis of AD.
作者
刘俐杰
丁彬彬
邓飞飞
周少军
张启芳
徐坚
余德军
柏华
Liu Lijie;Ding Binbin;Deng Feifei(Department of Neurology,the Third Affiliated Hospital of Guizhou Medical University,Duyun 558000,China;Department of Neurology,Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)
出处
《华中科技大学学报（医学版）》
CAS
CSCD
北大核心
2018年第2期218-221,共4页
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金
贵州省卫生计生委基金资助项目(No.gzwkj 2015-1-042)
贵州省科技厅课题(No.黔科合基础[2016-1131])
