水飞蓟素和瑞舒伐他汀对血脂异常的阿尔茨海默病患者淀粉样蛋白携带者水平的影响：一项双盲安慰剂对照随机临床试验。

Effects silymarin and rosuvastatin on amyloid-carriers level in dyslipidemic Alzheimer's patients: A double-blind placebo-controlled randomized clinical trial.

作者信息

Rustamzadeh Auob, Sadigh Nader, Vahabi Zahra, Khamseh Fatemeh, Mohebi Nafiseh, Ghobadi Zahra, Moradi Fatemeh

机构信息

Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Department of Anatomical Sciences, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.

出版信息

IBRO Neurosci Rep. 2024 Jul 20;17:108-121. doi: 10.1016/j.ibneur.2024.07.002. eCollection 2024 Dec.

DOI:10.1016/j.ibneur.2024.07.002

PMID:39139290

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11321388/

Abstract

PURPOSE

The production/excretion rate of Amyloid-β (Aβ) is the basis of the plaque burden in alzheimer's disease (AD), which depends on both central and peripheral clearance. In this study, the effect of silymarin and rosuvastatin on serum markers and clinical outcomes in dyslipidemic AD patients was investigated.

METHODS

Participants (n=36) were randomized to silymarin (140 mg), placebo, and rosuvastatin 10 mg orally three times a day for 6 months. Serum collection and clinical outcome tests were performed at baseline and after completion of treatment. Lipid profile markers, oxidative stress markers, Aβ/Aβ ratio, and Soluble Low-density lipoprotein receptor-Related Protein-1 (sLRP1)/Soluble Receptor for Advanced Glycation End Products (sRAGE) ratio were measured.

RESULTS

There was a statistically significant increase in Δ-high density lipoprotein (ΔHDL) between silymarin and placebo (P<0.000) and also between rosuvastatin and placebo (p=0.044). The level of Δ-triglycerides (ΔTG) in the silymarin group has a significant decrease compared to both the placebo and the rosuvastatin group (p<0.000 and p=0.036, respectively). The Δ-superoxide dismutase (ΔSOD) level in the silymarin group compared to placebo and rosuvastatin had a significant increase (p<0.000 and p=0.008, respectively). The ΔAβ/Aβ in the silymarin group compared to both the placebo and rosuvastatin groups had a significant increase (p<0.05). There was an inverse relationship between ΔTG and ΔAβ/Aβ (p=-0.493 and p=0.004). ΔAβ/Aβ has a direct statistical relationship with ΔSOD marker (p=0.388 and p=0.031). Also, there was a direct correlation between the level of ΔAβ/Aβ and ΔsLRP1/sRAGE (p=0.491 and p=0.005).

CONCLUSION

Our study showed the relationship between plasma lipids, especially ΔTG and ΔHDL, with ΔAβ/Aβ in dyslipidemic AD patients, and modulation of these lipid factors can be used to monitor the response to treatments.

摘要

目的

淀粉样β蛋白（Aβ）的生成/排泄率是阿尔茨海默病（AD）斑块负荷的基础，其取决于中枢和外周清除。本研究调查了水飞蓟宾和瑞舒伐他汀对血脂异常AD患者血清标志物和临床结局的影响。

方法

参与者（n = 36）被随机分为水飞蓟宾组（140毫克）、安慰剂组和瑞舒伐他汀组（10毫克，每日口服三次，共6个月）。在基线和治疗结束后进行血清采集和临床结局测试。测量血脂谱标志物、氧化应激标志物、Aβ/Aβ比值以及可溶性低密度脂蛋白受体相关蛋白1（sLRP1）/晚期糖基化终产物可溶性受体（sRAGE）比值。

结果

水飞蓟宾组与安慰剂组之间以及瑞舒伐他汀组与安慰剂组之间的Δ高密度脂蛋白（ΔHDL）有统计学显著升高（P < 0.000和p = 0.044）。水飞蓟宾组的Δ甘油三酯（ΔTG）水平与安慰剂组和瑞舒伐他汀组相比均有显著降低（分别为p < 0.000和p = 0.036）。水飞蓟宾组的Δ超氧化物歧化酶（ΔSOD）水平与安慰剂组和瑞舒伐他汀组相比有显著升高（分别为p < 0.000和p = 0.008）。水飞蓟宾组的ΔAβ/Aβ与安慰剂组和瑞舒伐他汀组相比均有显著升高（p < 0.05）。ΔTG与ΔAβ/Aβ之间存在负相关（p = -0.493和p = 0.004）。ΔAβ/Aβ与ΔSOD标志物存在直接统计学关系（p = 0.388和p = 0.031）。此外，ΔAβ/Aβ水平与ΔsLRP1/sRAGE之间存在直接相关性（p = 0.491和p = 0.005）。