摘要
基于中医“肾脑相济”理论,通过双样本孟德尔随机化探讨慢性肾脏病(chronic kidney disease, CKD)对阿尔茨海默病(Alzheimer′s disease, AD)的因果影响,分析补肾益精中药改善AD的可能机制。从CKD与AD核心病机“肾虚精亏髓减”密切相关为切入点,利用全基因组关联研究数据,以逆方差加权法(inverse variance weighting, IVW)分析为主,揭示CKD与AD的因果关联,并进行敏感性分析以评估结果的稳健性。为检查CKD对AD的因果影响,使用2个不同的AD数据集作为结局,运用尿白蛋白/肌酐比(urinary albumin-to-creatinine ratio, UACR)作为暴露进行补充分析。在此基础上进一步探讨补肾益精法改善AD的现代科学内涵。IVW分析显示,在不同的数据集中,CKD(ieu-b-2:OR=1.084,95%CI[1.011,1.163],P=0.024;ieu-b-5067:OR=1.001,95%CI[1.000,1.001],P=0.002)、UACR(ieu-b-2:OR=1.247,95%CI[1.021,1.522],P=0.031;ieu-b-5067:OR=1.001,95%CI[1.000,1.003],P=0.015)对AD均存在显著的因果影响,CKD增加了AD发生风险。敏感性分析证实了该结果的可靠性。遗传学研究表明,CKD对AD具有显著因果效应,提示控制CKD是防治AD的重要干预措施,在临床实践中进一步研究CKD对AD的风险至关重要。以上研究丰富了“肾脑相济”的理论内涵,深化了AD的病因学认识,为中医药从肾防治AD提供了思路与方向。
Based on the traditional Chinese medicine(TCM)theory of"kidney-brain interaction",a two-sample Mendelian randomization(MR)analysis was conducted to investigate the causal effects of chronic kidney disease(CKD)on Alzheimer's disease(AD)and analyze the potential mechanisms of kidney-tonifying and essence-replenishing TCM to improve AD.From the perspective that CKD is closely related to the core pathogenesis of AD,namely"kidney deficiency,essence loss,and marrow reduction",genomewide association study(GWAS)data was used,with the inverse variance weighting(IVW)method as the main approach to reveal the causal association between CKD and AD.Sensitivity analysis was conducted to evaluate the robustness of the results.To further investigate the causal effects of CKD on AD,two different AD datasets were used as outcomes,and the urinary albumin-to-creatinine ratio(UACR)data was used as the exposure for a supplementary analysis.On this basis,the modern scientific mechanism of the kidney-tonifying and essence-replenishing method for improving AD was further explored.The IVW analysis show that CKD(ieu-b-2:OR=1.084,95%CI[1.011,1.163],P=0.024;ieu-b-5067:OR=1.001,95%CI[1.000,1.001],P=0.002)and UACR(ieu-b-2:OR=1.247,95%CI[1.021,1.522],P=0.031;ieu-b-5067:0R=1.001,95%CI[1.000,1.003],P=0.015)both have significant causal effects on AD in different datasets,with CKD increasing the risk of AD.The sensitivity analysis further confirmed the reliability of the results.Genetic studies have shown that CKD has a significant causal effect on AD,suggesting that controlling CKD is an important intervention measure for preventing and treating AD.Therefore,further research on CKD's role in AD is crucial in clinical practice.The research enriches the theoretical implication of"kidney-brain interaction",deepens the understanding of AD'etiology,and provides further insights and directions for the prevention and treatment of AD with TCM,specifically from a kidney-based perspective.
作者
陈森林
王志晨
陈耿钊
郑杭彬
黄赛娥
CHEN Sen-lin;WANG Zhi-chen;CHEN Geng-zhao;ZHENG Hang-bin;HUANG Sai-e(Rehabilitation Hospital Afiliated to Fujian University of Traditional Chinese Medicine,Fuzhou 350003,China;Key Laboratory of Rehabilitation Technology of Fujian Province,Fuzhou 350003,China;Fujian Provincial Key Laboratory of Cognitive Function Rehabilitation,Fuzhou 350003,China;Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)
出处
《中国中药杂志》
北大核心
2025年第12期3431-3440,共10页
China Journal of Chinese Materia Medica
基金
福建省认知功能康复重点实验室开放课题(重点项目)(XKF2023006)
福建省自然科学基金项目(2021J01954)
福建省卫健委科技计划项目(2021CXA040)。
关键词
阿尔茨海默病
慢性肾脏病
“肾脑相济”
孟德尔随机化
补肾益精
Alzheimer's disease
chronic kidney disease
"kidney-brain interaction"
Mendelian randomization
kidney-tonifying and essence-replenishing
