水飞蓟宾加剧甘油诱导的急性肾损伤大鼠中 p53 介导的肾小管细胞凋亡。

Silymarin exacerbates p53-mediated tubular apoptosis in glycerol-induced acute kidney injury in rats.

机构信息

Division of Nephrology, Department of Medicine, Faculty of Medical Sciences, State University of Campinas, 04014-012 São Paulo, Brazil.

出版信息

Ren Fail. 2010 Jun;32(5):623-32. doi: 10.3109/08860221003778064.

DOI:10.3109/08860221003778064

PMID:20486847

Abstract

BACKGROUND/AIMS: Silymarin is an herbal extract with antioxidant properties that can reduce oxidative stress-mediated injuries in murine models of liver, heart, and kidney diseases. Silymarin can also increase p53-mediated cellular apoptosis in vitro. We tested the effect of silymarin administration before glycerol-induced acute kidney injury (Gly-AKI) in rats.

METHODS

Renal function, tubular injury, oxidative stress, leukocytes infiltration, and renal expression of apoptosis regulating proteins (p53, p-p53, Bax, Bcl-2, survivin, and cleaved caspase-3) were evaluated 6 or 24 h after glycerol.

RESULTS

Silymarin exacerbated the renal impairment and tubular apoptosis but had no effect on tubular necrosis or renal leukocytes infiltration. Renal lipid and DNA peroxidation was increased after glycerol and silymarin did not reduce oxidative stress. Proteins p53, p-p53, and proapoptotic Bax were upregulated in Gly-AKI rats treated with silymarin, whereas anti-apoptotic Bcl-2 was reduced in this group. Cleaved caspase-3 was overexpressed in Gly-AKI rats, particularly when treated with silymarin. Survivin was less expressed in Gly-AKI than in controls, but this deficit was not aggravated by silymarin.

CONCLUSION

The persistence of oxidative stress, inflammatory reaction, and tubular necrosis, as well as exacerbation of p53-mediated tubular apoptosis, led to a more severe renal impairment in Gly-AKI rats treated with silymarin.

摘要

背景/目的：水飞蓟素是一种具有抗氧化特性的草药提取物，可减少肝、心和肾病模型中氧化应激介导的损伤。水飞蓟素还可以增加体外 p53 介导的细胞凋亡。我们在甘油诱导的急性肾损伤（Gly-AKI）大鼠模型中测试了水飞蓟素给药前的作用。

方法

在甘油后 6 或 24 小时评估肾功能、肾小管损伤、氧化应激、白细胞浸润和肾脏凋亡调节蛋白（p53、p-p53、Bax、Bcl-2、survivin 和 cleaved caspase-3）的表达。

结果

水飞蓟素加重了肾损伤和肾小管凋亡，但对肾小管坏死或肾白细胞浸润没有影响。甘油后肾脂质和 DNA 过氧化增加，水飞蓟素不能减轻氧化应激。用水飞蓟素治疗的 Gly-AKI 大鼠中 p53、p-p53 和促凋亡 Bax 蛋白上调，而抗凋亡 Bcl-2 减少。Cleaved caspase-3 在 Gly-AKI 大鼠中过表达，特别是在用水飞蓟素治疗时。与对照组相比，Gly-AKI 中的 survivin 表达减少，但水飞蓟素并未加剧这种缺陷。