半胱胺可预防亚硒酸盐诱导白内障大鼠模型晶状体混浊的发展。

Cysteamine prevents the development of lens opacity in a rat model of selenite-induced cataract.

机构信息

Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Invest Ophthalmol Vis Sci. 2012 Mar 15;53(3):1452-9. doi: 10.1167/iovs.11-8636.

DOI:10.1167/iovs.11-8636

PMID:22281827

Abstract

PURPOSE

The activation of transglutaminase 2 (TG2) by oxidative stress through TGFβ has been reported to play a crucial role in cataract formation. The authors investigated whether TG2 is involved in selenite-induced cataract formation in rats and whether cysteamine, a chemical inhibitor of TG2, can prevent cataract formation in this model.

METHODS

Intracellular TG2 activity was monitored in a human lens epithelial cell (HLE-B3) line and cultured rat lenses after treatment with selenite. Rat pups (13 days old) were injected subcutaneously with sodium selenite (Na(2)SeO(3); 20 μmol/kg) and intraperitoneally with cysteamine (30, 40, and 60 mg/kg) for 14 days. Lenses were evaluated photographically at days 7 and 14. The concentrations of malondialdehyde and glutathione in the lenses were determined.

RESULTS

In HLE-B3 cells or rat lenses, selenite induced intracellular TG activity, which was inhibited by cysteamine. In selenite-treated rats, the rate of cataract formation was significantly reduced by cysteamine (P < 0.001). The mean cataract area in the lenses of cysteamine-treated rats was smaller than that of control rats (P < 0.01). The levels of total and reduced glutathione in the lenses of cysteamine-treated rats extracted at day 14 were higher than those of control rats.

CONCLUSIONS

Cysteamine suppresses cataract formation induced by selenite in rats, suggesting that cysteamine can be used as a pharmaceutical intervention to prevent or delay cataract formation.

摘要

目的

有报道称，氧化应激通过 TGFβ激活转谷氨酰胺酶 2（TG2）在白内障形成中起着关键作用。作者研究了 TG2 是否参与亚硒酸钠诱导的大鼠白内障形成，以及化学抑制剂半胱胺是否可以预防该模型中的白内障形成。

方法

用亚硒酸钠处理人晶状体上皮细胞（HLE-B3）系和培养的大鼠晶状体后，监测细胞内 TG2 活性。将 13 天大的大鼠幼仔（大鼠幼仔）皮下注射亚硒酸钠（Na2SeO3；20 μmol/kg），腹腔内注射半胱胺（30、40 和 60 mg/kg），共 14 天。在第 7 天和第 14 天拍摄晶状体照片进行评估。测定晶状体中丙二醛和谷胱甘肽的浓度。

结果

在 HLE-B3 细胞或大鼠晶状体中，亚硒酸钠诱导细胞内 TG 活性，半胱胺可抑制其活性。在亚硒酸钠处理的大鼠中，半胱胺显著降低白内障形成率（P <0.001）。与对照组相比，半胱胺处理组大鼠晶状体的平均白内障面积较小（P <0.01）。半胱胺处理组大鼠晶状体中总谷胱甘肽和还原型谷胱甘肽的水平在第 14 天提取时高于对照组。