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首页> 外文期刊>The Journal of Pharmacology and Experimental Therapeutics: Official Publication of the American Society for Pharmacology and Experimental Therapeutics >Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways
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Notoginsenoside R1 Protects against Neonatal Cerebral Hypoxic-Ischemic Injury through Estrogen Receptor-Dependent Activation of Endoplasmic Reticulum Stress Pathways

机译：三七皂甙R1通过内质网应激途径的雌激素受体依赖性激活来保护新生儿脑缺氧缺血性损伤

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摘要

Notoginsenoside R1 (NGR1) is a phytoestrogen that is isolated from Panax notoginseng. It is used in China to treat many diseases, including hypoxic-ischemic encephalopathy (HIE), and it has been shown to target estrogen receptors. Endoplasmic reticulum (ER) stress plays an important role in the development of cell apoptosis during ischemia, and ER stress is known to be regulated by estrogen; however, the neuroprotective mechanisms of NGR1 in neonatal HIE is unclear. In this study, oxygenglucose deprivation/reoxygenation (OGD/R) in primary cortical neurons and unilateral ligation of the common carotid artery (CCL), followed by exposure to a hypoxic environment in 7-day-old postnatal Sprague-Dawley rats were used to mimic HIE episodes. Potential neuroprotective effects of NGR1 against neonatal HIE and its mechanisms were examined. After HIE conditions in vitro and in vivo, we administered NGR1 or the estrogen receptor inhibitor ICI-182780 and measured cell apoptosis, brain injury by MTT assay, TTC stain, and so forth. Expression of estrogen receptors alpha (ER alpha) and beta (ER beta), ER stress-associated proteins was detected by Western blot upon stimulation with HIE, NGR1, or ICI-182780. Results showed that after HIE, ER chaperone GRP78 was activated, ER stress-associated proapoptotic proteins (CHOP, PERK, ERO1-alpha, and IRE1 alpha) were increased, caspase-12 was increased, and BCL-2 was decreased. The ER stress response and neuronal apoptosis were attenuated by NGR1 treatment. However, neuroprotective properties of NGR1 against HIE-induced apoptosis and ER stress were attenuated by ICI-182780. These results suggest that NGR1 may be an effective treatment of HIE by reducing ER stress-induced neuronal apoptosis and brain injury via estrogen receptors.
机译：三七皂苷R1（NGR1）是从三七中分离出来的一种植物雌激素。在中国，它被用于治疗多种疾病，包括缺氧缺血性脑病（HIE），并且已证明其靶向雌激素受体。内质网应激在缺血过程中细胞凋亡的发展中起着重要作用，并且已知雌激素调节内质网应激。然而，NGR1在新生儿HIE中的神经保护机制尚不清楚。在这项研究中，初级皮层神经元的氧葡萄糖剥夺/复氧（OGD / R）和颈总动脉（CCL）的单侧结扎，然后在7天大的出生后Sprague-Dawley大鼠中暴露于低氧环境下，模仿HIE情节。研究了NGR1对新生儿HIE的潜在神经保护作用及其机制。在体内和体外HIE条件后，我们给予NGR1或雌激素受体抑制剂ICI-182780并通过MTT分析，TTC染色等方法测量细胞凋亡，脑损伤。用HIE，NGR1或ICI-182780刺激后，通过Western blot检测雌激素受体α（ER alpha）和β（ER beta），ER应激相关蛋白的表达。结果表明，HIE后，ER伴侣GRP78被激活，ER应激相关的凋亡蛋白（CHOP，PERK，ERO1-alpha和IRE1 alpha）增加，caspase-12增加，BCL-2减少。 NGR1处理可减轻ER应激反应和神经元凋亡。但是，ICI-182780减弱了NGR1对HIE诱导的细胞凋亡和ER应激的神经保护作用。这些结果表明，NGR1可能通过减少雌激素受体引起的内质网应激诱导的神经元凋亡和脑损伤而有效治疗HIE。

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