【摘要】 目的探讨犬尿氨酸(KYN)通路主要代谢产物犬尿喹啉酸(KYNA)和3-羟基犬尿氨酸(3-HK)与AD的关系,以及KYN通路限速酶犬尿氨酸3-单加氧酶(KMO)基因多态性与AD的相关性。方法选取AD患者198例为AD组和健康体检者192例为对照组,采用简易智能状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)、日常生活活动能力量表(ADL)、临床痴呆评定量表(CDR)评估,检测各组KMOrs2275163、rs1053230等位基因频率和基因型频率。结果 AD组MMSE和MoCA评分明显低于对照组,ADL和CDR评分明显高于对照组(P<0.05,P<0.01)。AD组血浆KYN水平明显低于对照组,KYNA、3-HK及3-HK/KYN明显高于对照组[(1.2±0.2)mmol/L vs(1.3±0.2)mmol/L,P=0.043;(40.0±8.8)nmol/L vs(28.4±9.2)nmol/L,P=0.036;(108.5±14.6)nmol/L vs(35.2±5.6)nmol/L,P=0.011;(94.3±11.9)vs(28.9±9.5),P=0.016]。对照组与AD组rs2275163、rs1053230等位基因频率及基因型频率比较,差异无统计学意义(P>0.05)。结论 KYN通路代谢产物水平在AD患者中发生变化,在AD发病过程中可能发挥作用,可能成为AD诊断的血清学标志物。更多还原

【Abstract】 Objective To study the relationship of kynurenic acid(KYNA),3-hydroxy kynurenine(3-HK) and 3-monooxygenase(KMO) gene polymorphisms with AD.Methods One hundred and ninety-eight AD patients served as an AD group and 192 healthy persons who underwent physical examination served as a control group.The patients were assessed according to their MMSE scale,MoCA scale,ADL scale and CDR scale scores.The frequency of allelic gene and genotypes of KMO gene polymorphism at rs2275163 and rs1053230 was detected.Results The MMSE scale score and MoCA scale score were significantly lower while the ADL scale score and CDR scale sore were significant higher in AD group than in control group(P<0.05,P<0.01).The serum levels of KYN were significantly lower while those of KYNA and 3-HK were significantly higher in AD group than in control group(1.2±0.2 mmol/L vs 1.3±0.2 mmol/L,P=0.043;40.0±8.8 nmol/L vs 28.4±9.2 nmol/L,P=0.036;108.5±14.6 nmol/L vs 35.2±5.6 nmol/L,P=0.011;94.3±11.9 vs 28.9±9.5,P=0.016).No significant difference was detected in frequency of allelic genes(rs2275163 and rs1053230) and genotypes between the two groups(P>0.05).Conclusion Changes of serum metabolite level in KYN pathway of AD patients play a role in pathophysiology of AD and can be used as a serum biomarker in diagnosis of AD.更多还原