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乙酰牛磺酸镁和牛磺酸对内皮素-1诱导的大鼠视网膜亚硝化应激的影响。

Effect of Magnesium Acetyltaurate and Taurine on Endothelin1-Induced Retinal Nitrosative Stress in Rats.

作者信息

Nor Arfuzir Natasha Najwa, Agarwal Renu, Iezhitsa Igor, Agarwal Puneet, Sidek Sabrilhakim, Spasov Alexander, Ozerov Alexander, Mohd Ismail Nafeeza

机构信息

a Center for Neuroscience Research, Faculty of Medicine , Universiti Teknologi MARA Sungai Buloh Campus , Selangor , Malaysia.

b Volgograd State Medical University, Research Institute of Pharmacology , Volgograd , Russia.

出版信息

Curr Eye Res. 2018 Aug;43(8):1032-1040. doi: 10.1080/02713683.2018.1467933. Epub 2018 May 8.

Abstract

PURPOSE

Retinal ganglion cell apoptosis in glaucoma is associated with elevated levels of endothelin-1 (ET1), a potent vasoconstrictor. ET1-induced retinal ischemia leads to altered expression of nitric oxide synthase (NOS) isoforms leading to increased formation of nitric oxide (NO) and retinal nitrosative stress. Since magnesium (Mg) is known to improve endothelial functions and reduce oxidative stress and taurine (TAU) possesses potent antioxidant properties, we investigated the protective effects of magnesium acetyltaurate (MgAT) against ET1-induced nitrosative stress and retinal damage in rats. We also compared the effects of MgAT with that of TAU alone.

METHODS

Sprague Dawley rats were intravitreally injected with ET1. MgAT and TAU were administered as pre-, co-, or posttreatment. Subsequently, the expression of NOS isoforms was detected in retina by immunohistochemistry, retinal nitrotyrosine level was estimated using ELISA, and retinal cell apoptosis was detected by TUNEL staining.

RESULTS

Intravitreal ET1 caused a significant increase in the expressions of nNOS and iNOS while eNOS expression was significantly reduced compared to vehicle treated group. Administration of both MgAT and TAU restored the altered levels of NOS isoform expression, reduced retinal nitrosative stress and retinal cell apoptosis. The effect of MgAT, however, was greater than that of TAU alone.

CONCLUSIONS

MgAT and TAU prevent ET1-induced retinal cell apoptosis by reducing retinal nitrosative stress in Sprague Dawley rats. Addition of TAU to Mg seems to enhance the efficacy of TAU compared to when given alone. Moreover, the pretreatment with MgAT/TAU showed higher efficacy compared to co- or posttreatment.

摘要

目的

青光眼患者视网膜神经节细胞凋亡与强效血管收缩剂内皮素 -1(ET1)水平升高有关。ET1 诱导的视网膜缺血会导致一氧化氮合酶(NOS)亚型表达改变,从而导致一氧化氮(NO)生成增加和视网膜亚硝化应激。由于已知镁(Mg)可改善内皮功能并降低氧化应激,且牛磺酸(TAU)具有强大的抗氧化特性,我们研究了乙酰半胱氨酸镁(MgAT)对 ET1 诱导的大鼠亚硝化应激和视网膜损伤的保护作用。我们还比较了 MgAT 与单独使用 TAU 的效果。

方法

将 ET1 玻璃体内注射到 Sprague Dawley 大鼠体内。MgAT 和 TAU 作为预处理、联合处理或后处理给药。随后,通过免疫组织化学检测视网膜中 NOS 亚型的表达,使用 ELISA 估计视网膜硝基酪氨酸水平,并通过 TUNEL 染色检测视网膜细胞凋亡。

结果

与载体处理组相比,玻璃体内注射 ET1 导致 nNOS 和 iNOS 的表达显著增加,而 eNOS 表达显著降低。MgAT 和 TAU 的给药均恢复了 NOS 亚型表达的改变水平,降低了视网膜亚硝化应激和视网膜细胞凋亡。然而,MgAT 的效果大于单独使用 TAU 的效果。

结论

MgAT 和 TAU 通过降低 Sprague Dawley 大鼠的视网膜亚硝化应激来预防 ET1 诱导的视网膜细胞凋亡。与单独给药相比,在 Mg 中添加 TAU 似乎增强了 TAU 的疗效。此外,与联合处理或后处理相比,MgAT/TAU 的预处理显示出更高的疗效。

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