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莱菔硫烷在肾脏病的临床前模型中表现出强大的肾保护作用:系统评价和荟萃分析。

Sulforaphane exhibits potent renoprotective effects in preclinical models of kidney diseases: A systematic review and meta-analysis.

机构信息

Nutrition and Genomics Laboratory, Basic and Experimental Nutrition Department, Institute of Nutrition, Rio de Janeiro State University, 20550-900 Rio de Janeiro, Brazil.

Graduate Program in Pathology, Federal Fluminense University (UFF), Niterói, RJ, Brazil; Graduate Program in Nutrition Sciences, Federal Fluminense University (UFF), Niterói, RJ, Brazil.

出版信息

Life Sci. 2023 Jun 1;322:121664. doi: 10.1016/j.lfs.2023.121664. Epub 2023 Apr 5.

DOI:10.1016/j.lfs.2023.121664
PMID:37023957
Abstract

AIMS

Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, has received extensive attention as a natural activator of the Nrf2/Keap1 cytoprotective pathway. In this review, a meta-analysis and systematic review of the renoprotective effects of SFN were performed in various preclinical models of kidney diseases.

MAIN METHODS

The primary outcome was the impact of SFN on renal function biomarkers (uremia, creatininemia, proteinuria or creatinine clearance) and secondary outcomes were kidney lesion histological indices/kidney injury molecular biomarkers. The effects of SFN were evaluated according to the standardized mean differences (SMDs). A random-effects model was applied to estimate the overall summary effect.

KEY FINDINGS

Twenty-five articles (out of 209 studies) were selected from the literature. SFN administration significantly increased creatinine clearance (SMD +1.88 95 % CI: [1.09; 2.68], P < 0.0001, I = 0 %) and decreased the plasma creatinine (SMD -1.24, [-1.59; -0.88], P < 0.0001, I = 36.0 %) and urea (SMD -3.22 [-4.42, -2.01], P < 0.0001, I = 72.4 %) levels. SFN administration (median dose: 2.5 mg/kg, median duration: 3 weeks) significantly decreased urinary protein excretion (SMD -2.20 [-2.68; -1.73], P < 0.0001, I = 34.1 %). It further improved two kidney lesion histological indices namely kidney fibrosis (SMD -3.08 [-4.53; -1.63], P < 0.0001, I = 73.7 %) and glomerulosclerosis (SMD -2.24 [-2.96; -1.53], P < 0.0001, I = 9.7 %) and decreased kidney injury molecular biomarkers (SMD -1.51 [-2.00; -1.02], P < 0.0001, I = 0 %).

SIGNIFICANCE

These findings provide new insights concerning preclinical strategies for treating kidney disease or kidney failure with SFN supplements and should stimulate interest in clinical evaluations of SFN in patients with kidney disease.

摘要

目的

萝卜硫素(SFN)是十字花科蔬菜中天然存在的异硫氰酸盐,作为 Nrf2/Keap1 细胞保护途径的天然激活剂,受到了广泛关注。本综述通过元分析和系统评价,评估 SFN 在各种肾脏疾病的临床前模型中的肾脏保护作用。

方法

主要结局是 SFN 对肾功能生物标志物(尿素、肌酸酐、蛋白尿或肌酐清除率)的影响,次要结局是肾脏病变组织学指标/肾脏损伤分子生物标志物。SFN 的作用根据标准化均数差(SMD)进行评估。采用随机效应模型估计汇总效应。

主要发现

从文献中筛选出 25 篇文章(来自 209 项研究)。SFN 给药可显著增加肌酐清除率(SMD+1.88,95%CI:[1.09;2.68],P<0.0001,I=0%),降低血浆肌酐(SMD-1.24,[-1.59;-0.88],P<0.0001,I=36.0%)和尿素(SMD-3.22,[-4.42;-2.01],P<0.0001,I=72.4%)水平。SFN 给药(中位数剂量:2.5mg/kg,中位数持续时间:3 周)可显著减少尿蛋白排泄(SMD-2.20,[-2.68;-1.73],P<0.0001,I=34.1%)。此外,它还改善了两个肾脏病变组织学指标,即肾脏纤维化(SMD-3.08,[-4.53;-1.63],P<0.0001,I=73.7%)和肾小球硬化(SMD-2.24,[-2.96;-1.53],P<0.0001,I=9.7%),并降低肾脏损伤分子生物标志物(SMD-1.51,[-2.00;-1.02],P<0.0001,I=0%)。

意义

这些发现为使用 SFN 补充剂治疗肾脏疾病或肾衰竭的临床前策略提供了新的见解,应激发对 SFN 在肾病患者中的临床评估的兴趣。

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