Studies to elucidate the effect and antiapoptotic mechanism of 2-ethyl-3-hydroxy-6- methylpyridine-n-acetyltaurinate in a rat model of retinal ischemia–reperfusion

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引用次数: 1

Abstract

Background: The study of possible ways of effective correction of retinal ischemia-reperfusion injury, which accompanies a number of eye diseases, is relevant today. The aim of the study: To study the retinoprotective effect and antiapoptotic mechanism of 2-Ethyl-3-hydroxy-6-methyl-pyridine-N-acetyltaurinate (EHMP-NAT) in a rat model of retinal ischemia–reperfusion (I/R). Materials and methods: A pathology model with an increase in intraocular pressure (IOP) to 110 mmHg was used. The retinoprotective effect of EHMP-NAT at a dose of 4.4 mg/kg/day, in comparison with emoxipine and taurine in equimolar doses, was estimated by the changes in the retinal microcirculation, electroretinograms (the b/a coefficient), and retinal caspase-3, NF-κB p65, p53 gene expressions in Wistar rats. Results: The use of EHMP-NAT led to an increase in the retinal microcirculation level to 756.5 (median) perfusion units in comparison with emoxipine (p = 0.045) and taurine (p = 0.00029). The b/a coefficient increased in comparison with the group with emoxipine (p = 0.0099) and with the group with taurine (p = 0.015). In the group with EHMP-NAT, the caspase-3 gene expression decreased reliably in comparison with emoxipine (p = 0.0002) and with taurine (p = 0.0028); the NF-κB p65 gene expression decreased in comparison with emoxipine (p = 0.0009) and with taurine (p = 0.0022); the p 53 gene expression decreased in comparison with emoxipine (p = 0.0022) and with taurine (p = 0.0009). Conclusion: Based on the data obtained, in correction of retinal I/R by EHMP-NAT, improvements in the retinal microcirculation, functional state, and caspase-3, NF-κB p65, p53 gene expressions were more pronounced than in monotherapy with emoxipine or taurine.
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2-乙基-3-羟基-6-甲基吡啶-n-乙酰牛磺酸盐在大鼠视网膜缺血再灌注模型中的作用及其抗凋亡机制的研究
背景:视网膜缺血-再灌注损伤伴发多种眼病,研究有效矫正视网膜缺血-再灌注损伤的可能方法具有重要的现实意义。目的:研究2-乙基-3-羟基-6-甲基吡啶- n -乙酰牛磺酸盐(EHMP-NAT)对大鼠视网膜缺血再灌注(I/R)模型的视网膜保护作用及抗凋亡机制。材料与方法:采用眼内压升高至110 mmHg的病理模型。通过观察Wistar大鼠视网膜微循环、视网膜电图(b/a系数)和视网膜caspase-3、NF-κB p65、p53基因表达的变化,评估4.4 mg/kg/d剂量下EHMP-NAT与等摩尔剂量的莫西平、牛磺酸相比的视网膜保护作用。结果:与莫西平(p = 0.045)和牛磺酸(p = 0.00029)相比,使用EHMP-NAT可使视网膜微循环水平增加至756.5(中位)灌注单位。b/a系数高于莫西平组(p = 0.0099)和牛磺酸组(p = 0.015)。在EHMP-NAT组,与莫西平(p = 0.0002)和牛磺酸(p = 0.0028)相比,caspase-3基因表达可靠地下降;与莫西平(p = 0.0009)和牛磺酸(p = 0.0022)比较,NF-κB p65基因表达降低;与莫西平(p = 0.0022)和牛磺酸(p = 0.0009)相比,p53基因表达降低。结论:根据所获得的数据,EHMP-NAT矫正视网膜I/R时,视网膜微循环、功能状态及caspase-3、NF-κB p65、p53基因表达的改善比单纯使用莫西平或牛磺酸治疗更明显。
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