目标:莱茵硫烷(SFN),一种天然存在于十字花科蔬菜中的异硫氰酸盐,作为Nrf2/Keap1细胞保护途径的天然激活剂,受到了广泛的关注。在这次审查中,我们在各种肾脏疾病临床前模型中对SFN的肾脏保护作用进行了荟萃分析和系统评价.
方法:主要结果是SFN对肾功能生物标志物的影响(尿毒症,肌酐血症,蛋白尿或肌酐清除率)和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。根据标准化平均差异(SMD)评估SFN的效果。应用随机效应模型来估计总体汇总效应。
结果:从文献中选择了25篇文章(共209项研究)。SFN管理显着增加肌酐清除率(SMD1.8895%CI:[1.09;2.68],P<0.0001,I2=0%)并降低血浆肌酐(SMD-1.24,[-1.59;-0.88],P<0.0001,I2=36.0%)和尿素(SMD-3.22[-4.42,-2.01],P<0.0001,I2=72.4%)水平。SFN给药(中位剂量:2.5mg/kg,中位持续时间:3周)尿蛋白排泄显着减少(SMD-2.20[-2.68;-1.73],P<0.0001,I2=34.1%)。它进一步改善了两个肾脏病变的组织学指标,即肾脏纤维化(SMD-3.08[-4.53;-1.63],P<0.0001,I2=73.7%)和肾小球硬化(SMD-2.24[-2.96;-1.53],P<0.0001,I2=9.7%)和降低肾损伤的分子生物标志物(SMD-1.51[-2.00;-1.02],P<0.0001,I2=0%)。
结论: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,并应激发对肾脏疾病患者SFN临床评估的兴趣。
OBJECTIVE: 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.
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.
RESULTS: 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, I2 = 0 %) and decreased the plasma creatinine (SMD -1.24, [-1.59; -0.88], P < 0.0001, I2 = 36.0 %) and urea (SMD -3.22 [-4.42, -2.01], P < 0.0001, I2 = 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, I2 = 34.1 %). It further improved two kidney lesion histological indices namely kidney fibrosis (SMD -3.08 [-4.53; -1.63], P < 0.0001, I2 = 73.7 %) and glomerulosclerosis (SMD -2.24 [-2.96; -1.53], P < 0.0001, I2 = 9.7 %) and decreased kidney injury molecular biomarkers (SMD -1.51 [-2.00; -1.02], P < 0.0001, I2 = 0 %).
CONCLUSIONS: 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.