The protective mechanism of Naja Naja atra venom on diabetic kidney disease.

IF 1.8 3区 医学 Q4 TOXICOLOGY
HongYu Lu, YaJuan Wu, Yan Xie, XiaoWei Li, Xian Ji, TianHui Jiang, XiaoXian Pei, ZhuYa Zhou
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引用次数: 0

Abstract

Background: Diabetic kidney disease (DKD) is a serious microvascular complication of diabetes that affects both type 1 and type 2 diabetes patients at a high incidence rate. Naja Naja atra venom (NNAV) has been shown to have protective effects and improved renal function in diabetic rats. However, its mechanism of action is still unclear. This study aims to unravel the effectiveness and mechanisms of NNAV on DKD.

Methods: We conducted in vitro experiments in which Human Kidney-2 (HK-2) cells were stimulated with high glucose, and exposed to varying concentrations of NNAV. Cell morphology, as well as α-SMA, TGF-β1, and E-cadherin levels, were analyzed using immunofluorescence and western blot. In vivo experiments involved a diabetic rat model, where varying concentrations of cobra α-neurotoxin (CTX) were administrated via gastric treatment. We observed and noted pathomorphological changes, measured biochemical and oxidative stress indices, and used western blot to assess podocin and nephrin levels.

Results: High glucose levels can induce a decrease in E-cadherin expression and an increase in α-SMA and transforming growth factor-β1 (TGF-β1) expression in HK-2 cells. NNAV can inhibit the transdifferentiation of HK-2 cells to myofibroblast (MyoF) in a high glucose environment and reduce the expression of TGF-β1. Cobra α-neurotoxin (CTX) can reduce urine protein in diabetes model rats at an early stage, which is dose-independent and has a time application range. CTX can regulate the expression of nephrin and podocin.

Conclusion: The present study indicates that CTX and NNAV attenuate STZ and high glucose-induced DKD. Its mechanisms of action are associated with inhibiting oxidative stress and TEMT. The study suggests that NNAV and CTX might be a potential therapeutic drug for treating DKD.

Naja Naja atra 毒液对糖尿病肾病的保护机制
背景:糖尿病肾病(DKD)是糖尿病的一种严重微血管并发症,1 型和 2 型糖尿病患者的发病率都很高。Naja Naja atra 毒液(NNAV)已被证明对糖尿病大鼠具有保护作用,并能改善其肾功能。然而,其作用机制仍不清楚。本研究旨在揭示 NNAV 对 DKD 的疗效和作用机制:我们进行了体外实验,用高糖刺激人肾-2(HK-2)细胞,并将其暴露于不同浓度的 NNAV。使用免疫荧光和 Western 印迹分析了细胞形态以及 α-SMA、TGF-β1 和 E-cadherin 水平。体内实验采用糖尿病大鼠模型,通过胃部处理给大鼠注射不同浓度的眼镜蛇α-神经毒素(CTX)。我们观察并记录了病理形态学变化,测量了生化和氧化应激指数,并使用 Western 印迹技术评估了荚膜蛋白和肾素水平:结果:高血糖水平可诱导 HK-2 细胞中 E-cadherin 表达减少、α-SMA 和转化生长因子-β1(TGF-β1)表达增加。NNAV 可抑制 HK-2 细胞在高糖环境中向肌成纤维细胞(MyoF)的转分化,并降低 TGF-β1 的表达。眼镜蛇α-神经毒素(CTX)能在早期降低糖尿病模型大鼠的尿蛋白,且与剂量无关,有一定的应用时间范围。CTX能调节肾素和荚膜蛋白的表达:本研究表明,CTX 和 NNAV 可减轻 STZ 和高糖诱导的 DKD。其作用机制与抑制氧化应激和 TEMT 有关。本研究表明,NNAV 和 CTX 可能是治疗 DKD 的潜在药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.80
自引率
8.30%
发文量
39
审稿时长
6-12 weeks
期刊介绍: Journal of Venomous Animals and Toxins including Tropical Diseases (JVATiTD) is a non-commercial academic open access publication dedicated to research on all aspects of toxinology, venomous animals and tropical diseases. Its interdisciplinary content includes original scientific articles covering research on toxins derived from animals, plants and microorganisms. Topics of interest include, but are not limited to:systematics and morphology of venomous animals;physiology, biochemistry, pharmacology and immunology of toxins;epidemiology, clinical aspects and treatment of envenoming by different animals, plants and microorganisms;development and evaluation of antivenoms and toxin-derivative products;epidemiology, clinical aspects and treatment of tropical diseases (caused by virus, bacteria, algae, fungi and parasites) including the neglected tropical diseases (NTDs) defined by the World Health Organization.
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