依帕司他对大鼠晶状体渗透性膨胀的抑制作用.pdfVIP

药学学报 Acta Pharmaceutica Sinica 2009, 44 ( 10) : 1107 1111 ·1107 · 依帕司他对大鼠晶状体渗透性膨胀的抑制作用 * 冀立霞, 沈 宁, 李彩娜, 刘 泉, 环 奕, 申竹芳 ( 中国医学科学院、北京协和医学院 物研究所, 北京 100050) 摘要: 依帕司他 (epalrestat, Epal) 是目前唯一上市的醛糖还原酶 (aldose reductase, AR) 抑制剂, 主要用于 糖尿病外周神经病变。本研究采用离体器官培养方法, 用半乳糖诱导大鼠晶状体发生明显渗透性膨胀, 模拟体内 糖尿病性白内障的病理过程, 考察依帕司他是否具有抑制晶状体渗透性膨胀的作用。研究结果显示, 依帕司他 (5 mol·L−1) 能够明显抑制离体培养晶状体渗透性膨胀的发生, 渗透性膨胀相关基因——AR 及水通道蛋白1 (aquaporins1, AQP 1) 在mRNA 及蛋白水平的高表达也有显著改善作用。该研究为临床应用依帕司他防治糖尿病 性白内障提供了参考。 关键词: 依帕司他; 醛糖还原酶; 晶状体; 渗透性膨胀; 白内障 中图分类号: R963 文献标识码:A 文章编号: 05 13-4870 (2009) 10-1107-05 Inhibition effect of epalrestat on rat lens osmotic expansion * JI Li-xia, SHEN Ning, LI Cai-na, LIU Quan, HUAN Yi, SHEN Zhu-fang (Institute of Materia Medica, Chinese Academy of M edical Sciences and Peking Union M edical College, Beij ing 100050, China) Abstract: Epalrestat is the unique aldose reductase inhibitor on the market, which was mainly used for the diabetic neuropathy. Lenses osmotic expansion could be induced by galactose to mimic the pathological process of diabetic cataract in vitro. In present study, we mainly investigated whether epalrestat possesses inhibitory effect on the lens osmotic expansion. The results indicated that epalrestat could not only markedly inhibit rat lens osmotic expansion in vitro, but also significantly reduced the high expression of the osmotic expansion