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三七总皂苷 R1 通过上调 Trx-1 对丙烯酰胺诱导的 PC12 神经毒性的神经保护作用。

Neuroprotective effects of notoginsenoside R1 by upregulating Trx-1 on acrylamide-induced neurotoxicity in PC12.

机构信息

Institute for Cancer Medicine and School of Basic Medical Sciences, Southwest Medical University, Luzhou, China.

The authors contributed equally to this work.

出版信息

Hum Exp Toxicol. 2020 Jun;39(6):797-807. doi: 10.1177/0960327120901586. Epub 2020 Jan 23.

DOI:10.1177/0960327120901586
PMID:31971015
Abstract

Acrylamide (ACR) is a water-soluble chemical that is commonly used in chemical and cosmetic manufacture. Many studies have been carried out to investigate the neurotoxicity mechanisms of ACR, resulting in oxidative stress and nerve damages. One of the commonly used traditional Chinese medicines is notoginsenoside R1 (NR1). However, its mitochondrial-mediated apoptotic effect caused in ACR-induced neurotoxicity has not been reported. Our results have shown that NR1 resisted the neurotoxicity induced by ACR by upregulating the levels of thioredoxin-1 (Trx-1) in Rat adrenal chromaffin cell tumor (PC12) cells. NR1 inhibited the increase in levels of Bax, caspase-9, and caspase-3, which was instigated by ACR. Moreover, NR1 inhibited the decrease in levels of B-cell lymphoma 2 and Trx-1 induced by ACR. The downregulation of Trx-1 aggravated the mitochondrial-mediated apoptosis and increased the expression of the above molecules, which was induced by ACR. In contrast, overexpression of Trx-1 attenuated the mitochondrial-mediated apoptosis and inhibited the expression of the mentioned molecules induced by ACR. Our results suggested that NR1 protected ACR-induced mitochondrial apoptosis by upregulating Trx-1.

摘要

丙烯酰胺(ACR)是一种水溶性化学物质,常用于化学和化妆品制造。已经进行了许多研究来探讨 ACR 的神经毒性机制,导致氧化应激和神经损伤。常用的中药之一是三七皂苷 R1(NR1)。然而,它在 ACR 诱导的神经毒性中的线粒体介导的凋亡作用尚未报道。我们的结果表明,NR1 通过上调大鼠肾上腺嗜铬细胞瘤肿瘤(PC12)细胞中硫氧还蛋白-1(Trx-1)的水平来抵抗 ACR 诱导的神经毒性。NR1 抑制了 ACR 诱导的 Bax、caspase-9 和 caspase-3 水平的增加。此外,NR1 抑制了 ACR 诱导的 B 细胞淋巴瘤 2 和 Trx-1 水平的降低。Trx-1 的下调加重了 ACR 诱导的线粒体介导的细胞凋亡,并增加了上述分子的表达。相反,Trx-1 的过表达减弱了 ACR 诱导的线粒体介导的细胞凋亡,并抑制了 ACR 诱导的上述分子的表达。我们的结果表明,NR1 通过上调 Trx-1 来保护 ACR 诱导的线粒体细胞凋亡。

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