Dietary wolfberry ameliorates retinal structure abnormalities in db/db mice at the early stage of diabetes.

Dietary wolfberry ameliorates retinal structure abnormalities in db/db mice at the early stage of diabetes.
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膳食枸杞可改善糖尿病早期 db/db 小鼠的视网膜结构异常。

DOI:
10.1258/ebm.2011.010400
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发表时间:
2011-09
期刊:
Experimental biology and medicine (Maywood, N.J.)
影响因子:
--
通讯作者:
Lin D
Lin D
中科院分区:
其他
文献类型:
--
作者:
Tang L;Zhang Y;Jiang Y;Willard L;Ortiz E;Wark L;Medeiros D;Lin D

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高血糖相关的氧化应激和/或随之而来的内质网应激是糖尿病视网膜病变发病机制的致病因素。饮食中的生物活性成分,减轻氧化应激可能作为潜在的化学预防剂,以防止或减缓疾病的进展。枸杞是一种传统的亚洲水果,多年来一直用于预防亚洲国家的老年性眼病。在这里,我们报告了饮食枸杞改善db/db小鼠2型糖尿病早期阶段的小鼠视网膜异常。给6周龄的雄性小鼠喂食含有或不含1%(kCal)枸杞的对照饮食8周。饮食枸杞恢复了db/db小鼠的整个视网膜的厚度,特别是内核层和感光层,以及视网膜色素上皮(RPE)的完整性和神经节细胞数量。全视网膜细胞裂解物的蛋白质印迹显示,添加枸杞降低了内质网(ER)应激生物标志物BiP、PERK、ATF 6和半胱氨酸蛋白酶-12的表达;并恢复了AMPK、硫氧还蛋白、Mn SOD和FOXO 3 α的活性。为了确定我们的观察结果是否是由于枸杞中玉米黄质和叶黄素的高含量,使用这些类胡萝卜素进行了额外的研究。利用人二倍体RPE细胞系ARPE-19,我们证明玉米黄质和叶黄素都可以模拟枸杞对AMPK、硫氧还蛋白、Mn SOD、FOXO 3 α活性的激活的预防作用,使细胞活性氧正常化,并减轻暴露于高糖挑战的ARPE-19细胞中的ER应激。AMPKα的siRNA敲低可消除玉米黄质的预防作用。这些结果表明,AMPK激活似乎在上调硫氧还蛋白和Mn SOD的表达,以及减轻细胞的氧化应激和/或内质网应激枸杞和玉米黄质和/或叶黄素发挥关键作用。总之,膳食枸杞对糖尿病小鼠视网膜的保护至少部分是由于玉米黄质和/或叶黄素。
Hyperglycemia-linked oxidative stress and/or consequent endoplasmic reticulum stress are the causative factors of pathogenesis of diabetic retinopathy. Dietary bioactive components which mitigate oxidative stress may serve as potential chemopreventative agents to prevent or slow down the disease progression. Wolfberry is a traditional Asian fruit consumed for years to prevent aging eye diseases in Asian countries. Here we report that dietary wolfberry ameliorated mouse retinal abnormality at the early stage of type 2 diabetes in db/db mice. Male mice at 6 weeks of age were fed the control diet with or without 1 % (kCal) wolfberry for 8 weeks. Dietary wolfberry restored the thickness of the whole retina, in particular the inner nuclear layer and photoreceptor layer, and the integrity of retinal pigment epithelia (RPE), and the ganglion cell number in db/db mice. Western blotting of whole retinal cell lysates revealed that addition of wolfberry lowered expression of endoplasmic reticulum (ER) stress biomarkers BiP, PERK, ATF6, and caspase-12; and restored AMPK, thioredoxin, Mn SOD, and FOXO3α activities. To determine if our observations were due to the high contents of zeaxanthin and lutein in wolfberry additional studies using these carotenoids were conducted. Using the human adult diploid RPE cell line ARPE-19 we demonstrated that both zeaxanthin and lutein could mimic wolfberry preventive effect on activation of AMPK, thioredoxin, Mn SOD, FOXO3α activities, normalize cellular reactive oxygen species, and attenuate ER stress in ARPE-19 cells exposed to a high glucose challenge. The zeaxanthin preventive effect was abolished by siRNA knockdown of AMPKα. These results suggested that AMPK activation appeared to play a key role in upregulated expression of thioredoxin and Mn SOD, and mitigation of cellular oxidative stress and/or ER stress by wolfberry and zeaxanthin and/or lutein. Taken together, dietary wolfberry on retinal protection in diabetic mice is, at least partially, due to zeaxanthin and/or lutein.
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