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木犀草素,一种芳烃受体拮抗剂,通过调节NLRP/NOX4信号通路减轻糖尿病视网膜病变:实验和分子对接研究

Luteolin, an aryl hydrocarbon receptor antagonist, alleviates diabetic retinopathy by regulating the NLRP/NOX4 signalling pathway: Experimental and molecular docking study.

作者信息

Yang Y, Zhou M, Liu H

机构信息

Department of Ophthalmology, Affiliated Zhongshan Hospital of Dalian University, 116001, Dalian, Liaoning, China.

出版信息

Physiol Int. 2021 Jun 18. doi: 10.1556/2060.2021.00148.

DOI:10.1556/2060.2021.00148
PMID:34143751
Abstract

OBJECTIVE

The present report evaluates the protective effects of luteolin against diabetic retinopathy (DR).

MATERIALS AND METHODS

Diabetes was induced in rats by i.p. administration of 60 mg/kg of streptozotocin (STZ), followed by treatment with luteolin for 4 weeks. The effects of luteolin were determined based on the blood glucose and cytokine levels, and parameters of oxidative stress in retinal tissue of DR rats. The diameter of retinal vessels was estimated by fundus photography. A Western blot assay was used to determine the expression of apoptotic proteins and Nod-like receptor 3 (NLRP3) pathway proteins in the retina of DR rats. A molecular docking study was performed to evaluate the interaction between luteolin and NLRP3.

RESULTS

The level of blood glucose was reduced in the luteolin-treated group compared with the DR group. Reductions in cytokines and oxidative stress were observed in the retinal tissues of the luteolin-treated group relative to the DR group. Moreover, treatment with luteolin reduced the expression of NLRP1, NOX4, TXNIP, and NLRP3 proteins, and ameliorated the altered expression of apoptotic proteins in the retina of DR rats.

CONCLUSION

In conclusion, luteolin prevents retinal apoptosis in DR rats by regulating the NLRP/NOX4 signalling pathway.

摘要

目的

本报告评估木犀草素对糖尿病视网膜病变(DR)的保护作用。

材料与方法

通过腹腔注射60mg/kg链脲佐菌素(STZ)诱导大鼠患糖尿病,随后用木犀草素治疗4周。根据血糖和细胞因子水平以及DR大鼠视网膜组织中的氧化应激参数来确定木犀草素的作用效果。通过眼底摄影估计视网膜血管直径。采用蛋白质免疫印迹法检测DR大鼠视网膜中凋亡蛋白和Nod样受体3(NLRP3)信号通路蛋白的表达。进行分子对接研究以评估木犀草素与NLRP3之间的相互作用。

结果

与DR组相比,木犀草素治疗组的血糖水平降低。相对于DR组,木犀草素治疗组的视网膜组织中细胞因子和氧化应激水平降低。此外,木犀草素治疗降低了DR大鼠视网膜中NLRP1、NOX4、TXNIP和NLRP3蛋白的表达,并改善了凋亡蛋白表达的改变。

结论

总之,木犀草素通过调节NLRP/NOX4信号通路预防DR大鼠的视网膜凋亡。

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