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Tilianin Protects Diabetic Retina through the Modulation of Nrf2/TXNIP/NLRP3 Inflammasome Pathways.
Journal of Environmental Pathology, Toxicology and Oncology ( IF 2.4 ) Pub Date : 2020-01-01 , DOI: 10.1615/jenvironpatholtoxicoloncol.2020032544
Yunda Zhang 1 , Zhao Gao 2 , Xiaohong Gao 1 , Zhigang Yuan 1 , Tao Ma 1 , Gaiyun Li 1 , Ximei Zhang 1
Affiliation  

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.

中文翻译:

Tilianin通过调节Nrf2 / TXNIP / NLRP3炎性途径来保护糖尿病视网膜。

氧化应激和炎症被认为是糖尿病性视网膜病进展和发展的主要原因。当前,核因子红系-2-相关因子2(Nrf2),硫氧还蛋白相互作用蛋白(TXNIP)和NLRP3炎症小体途径在氧化应激和炎症相关疾病的研究中越来越受到关注。另一方面,tilianin(TN)由于其各种药理特性而备受关注。基于这些研究的结果,进行了这项研究以检查TN对糖尿病大鼠视网膜的治疗效果。将大鼠任意分成三组:对照组,糖尿病组和糖尿病加TN(口服20mg / kg体重42天,口服)组。糖尿病大鼠补充TN,食物摄入,空腹血糖状况,糖基化血红蛋白(HbA1c)的水平大大降低,并且血清胰岛素状态显着增加。TN治疗糖尿病大鼠可增加Nrf2及其靶基因HO-1的mRNA表达,并显着降低丙二醛状态。相对于糖尿病大鼠,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)的活性增加。此外,向糖尿病大鼠施用TN导致TXNIP,NOD样受体蛋白3(NLRP3),含有CARD(ASC),caspase-1和IL-1β蛋白的凋亡相关斑点样蛋白表达降低,并降低视网膜中TXNIP,NLRP3,ASC和caspase-1蛋白的分布 此外,TN治疗改善了糖尿病大鼠视网膜的形态和形态变化。一起,所有这些发现提供了明确的证据,即糖尿病大鼠的TN治疗通过其降血糖,抗氧化剂和抗炎特性来减轻糖尿病视网膜的变化。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炎症小体途径发生的,这可能在糖尿病性视网膜病的治疗中具有治疗作用。
更新日期:2020-01-01
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