背景:在阿尔茨海默病和血管性痴呆中已经报道了一氧化氮(NO)合成的改变。然而,由于生物样品中NO的测量在分析上具有挑战性,另类,稳定的NO合成循环生物标志物可能有助于揭示痴呆新的病理生理机制和治疗靶点。
方法:我们对与NO合成相关的精氨酸代谢物的循环浓度进行了系统综述和荟萃分析,精氨酸瓜氨酸,不对称(ADMA)和对称(SDMA)二甲基精氨酸,和鸟氨酸,在阿尔茨海默病和血管性痴呆。我们在PubMed中搜索了相关研究,Scopus,和WebofScience从成立到2023年5月31日。JBI检查表和等级被用来评估偏见的风险和证据的确定性,分别。
结果:在14项选定的研究中,精氨酸和鸟氨酸浓度在组间没有显著差异.相比之下,与对照组相比,痴呆患者的ADMA明显升高(标准平均差,SMD=0.62,95%CI0.06-1.19,p=0.029),SDMA(SMD=0.70,95%CI0.34-1.35,p<0.001),和瓜氨酸浓度(SMD=0.50,95%CI0.08-0.91,p=0.018)。在亚组分析中,效应大小与使用胆碱酯酶抑制剂和/或抗精神病药物治疗ADMA显著相关,和潜在的疾病(阿尔茨海默病),研究大陆,瓜氨酸的分析方法。
结论:ADMA的改变,SDMA,和瓜氨酸,NO合成的生物标志物,可能有助于研究不同形式的痴呆症的病理生理学并确定新的治疗策略。(PROSPERO注册号:CRD42023439528)。
Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer\'s disease and vascular dementia. However, as the measurement of NO in biological samples is analytically challenging, alternative, stable circulatory biomarkers of NO synthesis may be useful to unravel new pathophysiological mechanisms and treatment targets in dementia.
We conducted a systematic
review and meta-analysis of the circulating concentrations of arginine metabolites linked to NO synthesis, arginine, citrulline, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine, and
ornithine, in Alzheimer\'s disease and vascular dementia. We searched for relevant studies in PubMed, Scopus, and Web of Science from inception to the 31st of May 2023. The JBI checklist and GRADE were used to assess the risk of bias and the certainty of evidence, respectively.
In 14 selected studies, there were no significant between-group differences in arginine and
ornithine concentrations. By contrast, compared to controls, patients with dementia had significantly higher ADMA (standard mean difference, SMD=0.62, 95% CI 0.06-1.19, p = 0.029), SDMA (SMD=0.70, 95% CI 0.34-1.35, p<0.001), and citrulline concentrations (SMD=0.50, 95% CI 0.08-0.91, p = 0.018). In subgroup analysis, the effect size was significantly associated with treatment with cholinesterase inhibitors and/or antipsychotics for ADMA, and underlying disorder (Alzheimer\'s disease), study continent, and analytical method for citrulline.
Alterations in ADMA, SDMA, and citrulline, biomarkers of NO synthesis, may be useful to investigate the pathophysiology of different forms of dementia and identify novel therapeutic strategies. (PROSPERO registration number: CRD42023439528).