School of Medicine, Guizhou University, Guiyang, Guizhou, China.
Department of Urology, Tongren City People's Hospital, Tongren, Guizhou, China.
Biol Trace Elem Res. 2023 Apr;201(4):1792-1805. doi: 10.1007/s12011-022-03275-7. Epub 2022 May 12.
Effects of selenoproteins on many renal diseases have been reported. However, their role in renal ischemia-reperfusion (I/R) injury is unclear. The present study was performed to investigate the impact of ebselen and renal I/R injury on the expression of selenoproteins. Sprague-Dawley rats were pretreated with or without ebselen (10 mg/kg) through a daily single oral administration from 3 days before renal I/R surgery. RT-qPCR (real-time quantitative PCR) was performed to determine the mRNA expression of 25 selenoprotein genes in the renal tissues. The expression levels of two selenoproteins, including GPX3 (glutathione peroxidase 3) and DIO1 (iodothyronine deiodinase 1), were evaluated by Western blot or/and IHF (immunohistofluorescence) assays. Furthermore, renal function, renal damage, oxidative stress, and apoptosis were assessed. The results showed that in renal I/R injury, the mRNA levels of 15 selenoprotein genes (GPX1, GPX3, GPX4, DIO1, DIO2, TXNRD2, TXNRD3, SEPHS2, MSRB1, SELENOF, SELENOK, SELENOO, SELENOP, SELENOS, and SELENOT) were decreased, whereas those of eight selenoprotein genes (GPX2, GPX6, DIO3, TXNRD1, SELENOH, SELENOM, SELENOV, and SELENOW) were increased. I/R also induced a reduction in the expression levels of GPX3 and DIO1 proteins. In addition, our results indicated that ebselen reversed the changes in those selenoprotein genes, excluding SELENOH, SELENOM, SELENOP, and SELENOT, in renal I/R injury and alleviated I/R-induced renal dysfunction, tissue damage, oxidative stress, and apoptosis. To our knowledge, this is the first study to investigate the changes of 25 mammalian selenoprotein genes in renal I/R injury kidneys. The present study also provided more evidence for the roles of ebselen against renal I/R injury.
已有研究报道，硒蛋白对许多肾脏疾病都有影响。但是，其在肾缺血再灌注（I/R）损伤中的作用尚不清楚。本研究旨在探讨依布硒啉和肾 I/R 损伤对硒蛋白表达的影响。Sprague-Dawley 大鼠在肾 I/R 手术前 3 天通过每日单次口服给予依布硒啉（10 mg/kg）预处理。通过实时定量 PCR（RT-qPCR）检测肾脏组织中 25 种硒蛋白基因的 mRNA 表达。通过 Western blot 或/和免疫荧光（IHF）检测两种硒蛋白（谷胱甘肽过氧化物酶 3 [GPX3]和碘甲状腺原氨酸脱碘酶 1 [DIO1]）的表达水平。此外，还评估了肾功能、肾损伤、氧化应激和细胞凋亡。结果表明，在肾 I/R 损伤中，15 种硒蛋白基因（GPX1、GPX3、GPX4、DIO1、DIO2、TXNRD2、TXNRD3、SEPHS2、MSRB1、SELENOF、SELENOK、SELENOO、SELENOP、SELENOS 和 SELENOT）的 mRNA 水平降低，而 8 种硒蛋白基因（GPX2、GPX6、DIO3、TXNRD1、SELENOH、SELENOM、SELENOV 和 SELENOW）的 mRNA 水平升高。I/R 还导致 GPX3 和 DIO1 蛋白表达水平降低。此外，我们的结果表明，依布硒啉逆转了肾 I/R 损伤中除 SELENOH、SELENOM、SELENOP 和 SELENOT 之外的这些硒蛋白基因的变化，并缓解了 I/R 诱导的肾功能障碍、组织损伤、氧化应激和细胞凋亡。据我们所知，这是第一项研究哺乳动物 25 种硒蛋白基因在肾 I/R 损伤肾脏中的变化。本研究还为依布硒啉对抗肾 I/R 损伤的作用提供了更多证据。
