硒对百草枯中毒大鼠肺损伤的抗氧化作用。

Antioxidant effects of selenium on lung injury in paraquat intoxicated rats.

机构信息

Department of Emergency Medicine, Seoul National University Hospital, Seoul, Korea.

出版信息

Clin Toxicol (Phila). 2012 Sep;50(8):749-53. doi: 10.3109/15563650.2012.708418.

DOI:10.3109/15563650.2012.708418

PMID:22924652

Abstract

CONTEXT

Paraquat (PQ) causes lethal intoxication by inducing oxidant injury to the lung. Selenium is a cofactor for glutathione peroxidase (GPx), which is one of the major endogenous antioxidant enzymes.

OBJECTIVE

To determine whether selenium post-treatment activates GPx, decreases lung injury, and improves survival in PQ intoxicated rats.

MATERIALS AND METHODS

Male Spraque-Dawley rats were categorized into three groups: sham (n = 6), PQ (n = 12), and PQ + Se (n = 12). In the PQ and PQ + Se groups, 50 mg/kg of PQ was administered intraperitoneally. After 10 minutes, 60 μg/kg of Se (PQ + Se) or saline (PQ) was administered via the tail vein. Six rats per group were euthanized 6 hours or 24 hours later. Lung tissues were harvested for the measurement of GPx activity, reduced glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) and for histological analysis. Using separated set of rats, survival of PQ (n = 10) and PQ + Se (n = 10) were observed for 72 hours.

RESULTS

GPx activity in the PQ group at the 6-hour and 24-hour time points was lower than in the sham group (p < 0.006). GPx activity in the PQ + Se group at the 6-hour and 24-hour time points was higher than in the PQ group at the same time (p < 0.006). GPx activity in the PQ + Se group at 24 hours was higher than at 6-hour time point and also higher than in the sham group (p < 0.006). The GSH/GSSG ratio in the PQ + Se group at 24 hours was lower than that in the sham group (p < 0.006). MDA levels in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). MDA levels at 24 hours in the PQ + Se group was lower than in the PQ group (p < 0.006). Acute lung injury (ALI) scores in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). ALI scores at 24 hours in the PQ + Se group were lower than in the PQ group. Survival rates did not differ between PQ and PQ + Se (p = 0.869).

CONCLUSION

Single dose of selenium post-treatment activates GPx and attenuates lipid peroxidation and lung injury early after paraquat intoxication, but does not improve 72 hours of survival.

摘要

背景

百草枯（PQ）通过诱导肺氧化损伤引起致命性中毒。硒是谷胱甘肽过氧化物酶（GPx）的辅助因子，GPx 是主要的内源性抗氧化酶之一。

目的

确定硒后处理是否激活 GPx、减轻肺损伤并提高百草枯中毒大鼠的存活率。

材料和方法

雄性 Spraque-Dawley 大鼠分为三组：假手术组（n = 6）、PQ 组（n = 12）和 PQ + Se 组（n = 12）。PQ 组和 PQ + Se 组大鼠均经腹腔注射 50mg/kg PQ。10 分钟后，通过尾静脉给予 60μg/kg Se（PQ + Se）或生理盐水（PQ）。每组 6 只大鼠于 6 小时或 24 小时后安乐死。采集肺组织测量 GPx 活性、还原型谷胱甘肽（GSH）、谷胱甘肽二硫化物（GSSG）和丙二醛（MDA）含量，并进行组织学分析。使用另一组大鼠，观察 PQ 组（n = 10）和 PQ + Se 组（n = 10）的 72 小时存活率。

结果

PQ 组在 6 小时和 24 小时时的 GPx 活性低于假手术组（p < 0.006）。PQ + Se 组在 6 小时和 24 小时时的 GPx 活性高于同一时间的 PQ 组（p < 0.006）。PQ + Se 组在 24 小时时的 GPx 活性高于 6 小时时，也高于假手术组（p < 0.006）。24 小时时 PQ + Se 组的 GSH/GSSG 比值低于假手术组（p < 0.006）。PQ 组在 6 小时和 24 小时时的 MDA 水平高于假手术组（p < 0.006）。PQ + Se 组在 24 小时时的 MDA 水平低于 PQ 组（p < 0.006）。PQ 组在 6 小时和 24 小时时的急性肺损伤（ALI）评分高于假手术组（p < 0.006）。PQ + Se 组在 24 小时时的 ALI 评分低于 PQ 组。PQ 组和 PQ + Se 组的存活率无差异（p = 0.869）。