Amelioration of Mouse Retinal Degeneration After Blue LED Exposure by Glycyrrhizic Acid-Mediated Inhibition of Inflammation
Amelioration of Mouse Retinal Degeneration After Blue LED Exposure by Glycyrrhizic Acid-Mediated Inhibition of Inflammation
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DOI：
10.3389/fncel.2019.00319
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发表时间：
2019-07-16
影响因子：
5.3
通讯作者：
Kim, In-Beom
中科院分区：
文献类型：
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作者：
Kim, Gyu Hyun;Paik, Sun-Sook;Kim, In-Beom
甘草酸（GA）是甘草（光果甘草）根和根茎中的主要成分，因其具有抗炎活性而被用作草药。 GA 被称为高迁移率族蛋白 1 (HMGB1) 的抑制剂，参与包括视网膜内神经病变在内的多种炎症性疾病的发病机制。在这项研究中，我们研究了 GA 对小鼠视网膜变性 (RD) 模型的影响，RD 是导致失明的主要原因。 RD 是通过暴露于蓝色发光二极管 (LED) 引起的。在功能评估中，视网膜电图显示，与未治疗的 RD 小鼠相比，RD 小鼠的 a 波和 b 波振幅均降低，而 GA 治疗的 RD 小鼠的 a 波和 b 波振幅显着增加（P < 0.05）。在组织学评估中，GA 处理保留了光感受器所在的外核层并减少了光感受器细胞死亡。与未处理的视网膜相比，GA处理的视网膜显示促炎细胞因子的表达显着降低，例如TNF-α、IL-6、IL-1β、CCL2和6、iNOS和COX-2（P < 0.05）。免疫组织化学显示，GA 处理的视网膜中 Iba-1 和 GFAP 表达显着降低，表明神经胶质反应和炎症降低。有趣的是，在未经处理的 RD 视网膜中 HMGB1 表达减少，而 GA 却相反地增加了其表达。这些结果表明，GA 通过抑制蓝色 LED 诱导的 RD 中的炎症来保留视网膜结构和功能，表明 GA 作为 RD 药物的潜在应用。此外，我们提出 HMGB1 在 RD 发病机制中具有潜在的视网膜保护功能。
Glycyrrhizic acid (GA) is a major component in the root and rhizomes of licorice (Glycyrrhiza glabra), which have been used as an herbal medicine, because of its anti-inflammatory activity. GA is known as an inhibitor of high-mobility group box 1 (HMGB1), which is involved in the pathogenesis of various inflammatory diseases including inner retinal neuropathy. In this study, we examined the effect of GA in a mouse model of retinal degeneration (RD), the leading cause of blindness. RD was induced by exposure to a blue light-emitting diode (LED). In functional assessment, electroretinography showed that the amplitudes of both a- and b-waves were reduced in RD mice, whereas they were significantly increased in GA-treated RD mice (P < 0.05), compared to those in non-treated RD animals. In histological assessment, GA treatment preserved the outer nuclear layer where photoreceptors reside and reduced photoreceptor cell death. GA-treated retinas showed significantly reduced expression of proinflammatory cytokines such as TNF-alpha, IL-6, IL-1 beta, CCL2 and 6, iNOS, and COX-2 (P < 0.05), compared to that in non-treated retinas. Immunohistochemistry showed that Iba-1 and GFAP expression was markedly reduced in GA-treated retinas, indicating decreased glial response and inflammation. Interestingly, HMGB1 expression was reduced in non-treated RD retinas whereas GA paradoxically increased its expression. These results demonstrate that GA preserves retinal structure and function by inhibiting inflammation in blue LED-induced RD, suggesting a potential application of GA as a medication for RD. In addition, we propose a potential retinal protective function of HMGB1 in the pathogenesis of RD.