Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China.
Department of Vitreoretinopathy, Shanxi Eye Hospital, Taiyuan, Shanxi, China; Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, China.
J Environ Pathol Toxicol Oncol. 2020;39(1):89-99. doi: 10.1615/JEnvironPatholToxicolOncol.2020032544.
Oxidative stress and inflammation are regarded as prime reasons for the progression and development of diabetic retinopathy. Currently, nuclear factor erythroid-2-related factor 2 (Nrf2), thioredoxin interacting protein (TXNIP) and NLRP3 inflammasome pathways are under increasing focus in research on oxidative stress and inflammation-related diseases. On the other hand, tilianin (TN) has received much attention because of its various pharmacological properties. Based on results of these studies, this investigation was performed to inspect the therapeutic efficiency of TN on the retina in diabetic rats. Rats were arbitrarily assigned to three groups: control group, diabetic group, and diabetic plus TN (20 mg/ kg body weight for 42 days, orally) group. TN supplementation in diabetic rats, their food intake, fasting blood glucose status, glycosylated hemoglobin (HbA1c) levels were drastically reduced, and there was a marked augmentation in serum insulin status. TN treatment of diabetic rats increased mRNA expression of Nrf2 and its target gene, HO-1, and noticeably decreased the malondialdehyde status. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX) were increased relative to diabetic rats. Furthermore, administering TN to the diabetic rats resulted in decreased expression of TXNIP, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1β proteins and decreased distribution of TXNIP, NLRP3, ASC, and caspase-1 proteins in retinas. In addition, TN treatment ameliorated morphological and morphometric changes in the retinas of diabetic rats. Together, all of these findings provide clear evidence that TN treatment of diabetic rats attenuated diabetic retinal changes through its hypoglycemic, antioxidant, and anti-inflammatory properties. The antioxidant and anti-inflammatory effects in diabetic retinas occur at least in part through the modulation of Nrf2/TXNIP/NLRP3 inflammasome pathways, which may have remedial benefits in the healing of diabetic retinopathy.
氧化应激和炎症被认为是糖尿病性视网膜病变进展和发展的主要原因。目前，核因子红细胞 2 相关因子 2（Nrf2）、硫氧还蛋白相互作用蛋白（TXNIP）和 NLRP3 炎性小体途径在氧化应激和炎症相关疾病的研究中受到越来越多的关注。另一方面，梣酮（TN）因其多种药理特性而受到广泛关注。基于这些研究的结果，本研究旨在检查 TN 对糖尿病大鼠视网膜的治疗效果。大鼠被任意分为三组：对照组、糖尿病组和糖尿病加 TN（20mg/kg 体重，口服，42 天）组。TN 补充剂可显著降低糖尿病大鼠的食物摄入量、空腹血糖状态、糖化血红蛋白（HbA1c）水平，并显著增加血清胰岛素水平。TN 治疗糖尿病大鼠可增加 Nrf2 及其靶基因 HO-1 的 mRNA 表达，并显著降低丙二醛水平。超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GPX）的活性相对于糖尿病大鼠增加。此外，给予糖尿病大鼠 TN 可降低 TXNIP、NOD 样受体蛋白 3（NLRP3）、凋亡相关斑点样蛋白含有 CARD（ASC）、半胱天冬酶-1 和 IL-1β 蛋白的表达，并降低 TXNIP、NLRP3、ASC 和半胱天冬酶-1 蛋白在视网膜中的分布。此外，TN 治疗可改善糖尿病大鼠视网膜的形态和形态计量学变化。综上所述，所有这些发现都为 TN 治疗糖尿病大鼠通过其降血糖、抗氧化和抗炎特性减轻糖尿病视网膜病变提供了明确的证据。糖尿病视网膜中的抗氧化和抗炎作用至少部分是通过调节 Nrf2/TXNIP/NLRP3 炎性小体途径实现的，这可能对糖尿病性视网膜病变的愈合有治疗益处。
