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防己诺林碱通过抑制晚期糖基化终产物受体(RAGE)-核因子-κB 轻链增强子的激活 B 细胞(NF-κB)通路改善链脲佐菌素(STZ)诱导的糖尿病大鼠的糖尿病视网膜病变。

Fangchinoline Ameliorates Diabetic Retinopathy by Inhibiting Receptor for Advanced Glycation End-Products (RAGE)-Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) Pathway in Streptozotocin (STZ)-Induced Diabetic Rats.

机构信息

Department of Ophthalmology, Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, China (mainland).

出版信息

Med Sci Monit. 2019 Feb 11;25:1113-1121. doi: 10.12659/MSM.912927.

DOI:10.12659/MSM.912927
PMID:30739905
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6380384/
Abstract

BACKGROUND Diabetic retinopathy (DR) is a macrovascular complication that occurs in diabetic patients. Conventional treatments for the management of DR have many limitations. Thus, the present investigation evaluated the protective effect of fangchinoline against diabetic retinopathy (DR). MATERIAL AND METHODS DR was induced by streptozotocin (STZ; 60 mg/kg; i.p.) and rats were treated with fangchinoline 1, 3, and 10 mg/kg for 16 weeks. DR was confirmed by determining the concentration of advanced glycation end-products (AGEs) and morphology of retinal tissues. Parameters of oxidative stress and expression of inflammatory cytokines and receptor for advanced glycation end-products (RAGE) in the retinal tissue were determined by Western blot assay and reverse transcription polymerase chain reaction (RT-PCR). Moreover enzyme-linked immunosorbent assay (ELISA) was used to determine the apoptosis index and activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in the retinal tissues. RESULTS Our study reveals that the concentration of glycosylated hemoglobin (HbA1c) and glucose in the plasma and AGEs in the retinal tissue were significantly reduced in the fangchinoline group compared to the DR group. Moreover, treatment with fangchinoline attenuated the altered retinal morphology and expression of inflammatory mediators and RAGE in the retinal tissues of DR rats. There was a significant (p<0.01) decrease in oxidative stress, activity of NF-κB, and apoptosis index in the fangchinoline group compared to the DR group of rats. CONCLUSIONS Our investigation shows that fangchinoline attenuates the apoptosis of retinal cells in STZ-induced diabetic retinopathy rats by inhibiting the RAGE/NF-κB pathway.

摘要

背景

糖尿病视网膜病变(DR)是一种发生在糖尿病患者中的大血管并发症。DR 的常规治疗方法存在许多局限性。因此,本研究评估了防己诺林碱对糖尿病视网膜病变(DR)的保护作用。

材料与方法

通过链脲佐菌素(STZ;60mg/kg;腹腔注射)诱导 DR,并用防己诺林碱 1、3 和 10mg/kg 治疗 16 周。通过测定晚期糖基化终产物(AGEs)的浓度和视网膜组织的形态来确认 DR。通过 Western blot 分析和逆转录聚合酶链反应(RT-PCR)测定视网膜组织中氧化应激参数和炎症细胞因子及晚期糖基化终产物受体(RAGE)的表达。此外,酶联免疫吸附试验(ELISA)用于测定视网膜组织中的细胞凋亡指数和核因子 kappa-轻链增强子的活性B 细胞(NF-κB)。

结果

我们的研究表明,与 DR 组相比,防己诺林碱组血浆中糖化血红蛋白(HbA1c)和葡萄糖浓度以及视网膜组织中 AGEs 明显降低。此外,防己诺林碱治疗可减轻 DR 大鼠视网膜组织中炎症介质和 RAGE 的改变以及视网膜形态。与 DR 组相比,防己诺林碱组氧化应激、NF-κB 活性和细胞凋亡指数显著降低(p<0.01)。

结论

我们的研究表明,防己诺林碱通过抑制 RAGE/NF-κB 通路减轻 STZ 诱导的糖尿病视网膜病变大鼠视网膜细胞的凋亡。

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Fangchinoline Ameliorates Diabetic Retinopathy by Inhibiting Receptor for Advanced Glycation End-Products (RAGE)-Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells (NF-κB) Pathway in Streptozotocin (STZ)-Induced Diabetic Rats.防己诺林碱通过抑制晚期糖基化终产物受体(RAGE)-核因子-κB 轻链增强子的激活 B 细胞(NF-κB)通路改善链脲佐菌素(STZ)诱导的糖尿病大鼠的糖尿病视网膜病变。
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