Effects of Glycyrrhizin Treatment on Diabetic Cornea.
Effects of Glycyrrhizin Treatment on Diabetic Cornea.
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DOI：
10.1089/jop.2020.0105
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发表时间：
2020-12
期刊：
影响因子：
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通讯作者：
M. Somayajulu;S. Mcclellan;Ahalya Pitchaikannu;D. Bessert;Li Liu;J. Steinle;L. Hazlett
中科院分区：
文献类型：
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作者：
M. Somayajulu;S. Mcclellan;Ahalya Pitchaikannu;D. Bessert;Li Liu;J. Steinle;L. Hazlett
目的：观察糖蛋白（GLY）对小鼠角膜上皮细胞（MCEC）及糖尿病小鼠角膜的影响。方法：采用MTT法检测MCEC在正常葡萄糖和高糖（HG）条件下的存活率。此外，C57 BL/6小鼠注射链脲佐菌素，对照组和糖尿病小鼠的一个子集在饮用水中接受GLY。在两种模型中，通过逆转录-聚合酶链反应（RT-PCR）检测促炎和氧化应激分子的mRNA和蛋白水平。使用人糖尿病角膜与对照角膜的离体研究使用RT-PCR和酶联免疫吸附测定分析促炎和氧化应激标志物。结果如下：GLY可保护HG诱导的细胞活力丧失，并显著降低HMGB 1、IL-1β、TLR 2、TLR 4、NLRP 3、COX 2、SOD 2、HO-1、GPX 2和GR 1。在体内，GLY治疗的糖尿病小鼠角膜显示CXCL 2、iNOS和上述所有分子的mRNA表达显著降低; GLY还降低HMGB 1和IL-1β蛋白（体外和体内）。使用糖尿病人角膜的离体研究显示，与正常年龄匹配的对照相比，炎症和氧化应激分子的mRNA水平升高（如上文针对体内所列）。与对照角膜相比，糖尿病患者角膜中HMGB 1和IL-1β的蛋白水平也升高。结论：这些数据提供了证据表明，GLY治疗减轻了MCEC体外和糖尿病小鼠角膜体内的炎症和氧化应激。离体数据支持小鼠与人类相比促炎和氧化应激数据的相似性，表明GLY治疗与患者护理相关。
Purpose: To test how glycyrrhizin (GLY) affects mouse corneal epithelial cells (MCEC) and the diabetic murine cornea. Methods: Viability of MCEC grown under normal or high glucose (HG) with/without GLY was tested by an MTT assay. In addition, C57BL/6 mice were injected with streptozotocin and a subset of control and diabetic mice received GLY in their drinking water. mRNA and protein levels of proinflammatory and oxidative stress molecules were tested by reverse transcription-polymerase chain reaction (RT-PCR) in both models. Ex vivo studies using human diabetic versus control corneas analyzed proinflammatory and oxidative stress markers using RT-PCR and enzyme-linked immunosorbent assay. Results: GLY protected against loss of cell viability induced by HG and significantly reduced HMGB1, IL-1β, TLR2, TLR4, NLRP3, COX2, SOD2, HO-1, GPX2, and GR1. In vivo, corneas of GLY-treated diabetic mice showed significantly decreased mRNA expression for CXCL2, iNOS, and all molecules listed above; GLY also lowered HMGB1 and IL-1β proteins (in vitro and in vivo). Ex vivo studies using diabetic human corneas revealed elevated mRNA levels of inflammatory and oxidative stress molecules (as listed above for in vivo) versus normal age-matched controls. Protein levels for HMGB1 and IL-1β also were elevated in diabetic human versus control corneas. Conclusions: The data provide evidence that GLY treatment attenuates inflammation and oxidative stress in vitro in MCEC and in vivo in the cornea of diabetic mice. Ex vivo data support the similarities of proinflammatory and oxidative stress data in mouse compared to human, suggesting that GLY treatment would have relevancy to patient care.