Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Integrated Research, Korea Institute of Oriental Medicine (KIOM), 483 Exporo, Yuseong-gu, Daejeon 305-811, Republic of Korea.
Evid Based Complement Alternat Med. 2011;2011. doi: 10.1155/2011/717921. Epub 2010 Sep 7.
Damage of lens epithelial cells (LECs) has been implicated in cataract formation. The aim of this study was to investigate the protective effect of KIOM-79, a combination of four plant extracts, on LECs. We examined the levels of advanced glycation end products (AGEs), nuclear factor-kappaB (NF-κB) activation and inducible nitric oxide synthase (iNOS) expression in LECs during cataract development using the Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. KIOM-79 was orally administered by gavage to ZDF rats once a day for 13 weeks. Apoptosis was detected by TUNEL assay, and NF-κB activation and iNOS expression were studied by southwestern histochemistry and immunohistochemistry, respectively. In diabetic cataractous lenses, TUNEL-positive LECs were markedly increased 20-fold, and AGEs were highly accumulated (2.7-fold) in LECs. In addition, both NF-κB activation, and iNOS expression were significantly enhanced 3- to 5-fold, respectively, compared to levels found in normal ZL rats. However, the administration of KIOM-79 delayed the development of diabetic cataracts and prevented LEC apoptosis (70%) through the inhibition of AGEs, NF-κB-activation and iNOS expression. These observations suggest that KIOM-79 is useful in inhibiting diabetic cataractogenesis and acts through an antiapoptotic mechanism to protect LECs from injury.
晶状体上皮细胞 (LEC) 的损伤与白内障的形成有关。本研究旨在探讨 KIOM-79(四种植物提取物的组合)对 LEC 的保护作用。我们使用 2 型糖尿病动物模型 Zucker 糖尿病肥胖 (ZDF) 大鼠,研究了白内障形成过程中 LEC 中晚期糖基化终产物 (AGEs)、核因子-κB (NF-κB) 激活和诱导型一氧化氮合酶 (iNOS) 的表达水平。KIOM-79 通过灌胃每天一次给予 ZDF 大鼠,共 13 周。通过 TUNEL 测定法检测细胞凋亡,通过西南印迹组织化学和免疫组织化学分别研究 NF-κB 激活和 iNOS 表达。在糖尿病性白内障晶状体中,TUNEL 阳性 LEC 显著增加 20 倍,LEC 中 AGEs 高度累积(2.7 倍)。此外,与正常 ZL 大鼠相比,NF-κB 激活和 iNOS 表达分别显著增强了 3 至 5 倍。然而,KIOM-79 的给药延缓了糖尿病性白内障的发展,并通过抑制 AGEs、NF-κB 激活和 iNOS 表达来防止 LEC 凋亡(70%)。这些观察结果表明,KIOM-79 可有效抑制糖尿病性白内障的发生,并通过抗凋亡机制保护 LEC 免受损伤。