Background Morbidity and mortality remain high for ischemic stroke victims, and at present these patients lack effective neuroprotective agents, which improve the cure rate. In recent years, studies have shown that pelargonidin has many biological actions. However, few studies are available regarding the pelargonidin treatment of cerebral ischemia. Methods The rat middle cerebral artery occlusion (MCAO) model was established to investigate the neuroprotective effect of pelargonidin on cerebral ischemia/reperfusion injury. Reperfusion was performed 2 h after ischemia; magnetic resonance imaging (MRI) and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining were used to measure the volume of cerebral ischemia. Both modified neurological severity scores (mNSSs) and Morris water maze test were used to assess the neurological functions. ELISA was applied to determine the levels of TNF-α, TGF-β, IL-6, IL-10, MDA, and SOD. The expression of Nuclear factor-E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) protein in brain tissue was measured by immunofluorescence and Western blot assays. Results The results showed that pelargonidin could effectively reduce the volume of cerebral ischemia and improve the neurological function in MCAO rats, thereby improving memory and learning ability. With the corresponding decreases in the expression of TNF-α, TGF-β, IL-6, and MDA, the level of IL-10 and SOD increased and also promoted the nuclear metastasis of Nrf2 and the expression of HO-1 in ischemic brain tissues. Conclusions Our data demonstrated that pelargonidin ameliorated neurological function deficits in MCAO rats, and its potential mechanism of action was associated with overexpression of the Nrf2/HO-1-signaling pathway. This study will provide a new approach to treat cerebral ischemia/reperfusion injury.

中文翻译：

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天竺葵素通过对 Nrf2/HO-1 通路的作用改善 MCAO 诱导的大鼠脑缺血/再灌注损伤

背景缺血性卒中患者的发病率和死亡率仍然很高，目前这些患者缺乏有效的神经保护剂，从而提高治愈率。近年来，研究表明，天竺葵素具有多种生物学作用。然而，很少有关于天竺葵素治疗脑缺血的研究。方法建立大鼠大脑中动脉闭塞（MCAO）模型，研究天竺葵素对脑缺血/再灌注损伤的神经保护作用。缺血后2小时进行再灌注；磁共振成像（MRI）和2, 3, 5-三苯基氯化四唑（TTC）染色用于测量脑缺血体积。改良的神经严重程度评分 (mNSS) 和莫里斯水迷宫测试均用于评估神经功能。ELISA用于测定TNF-α、TGF-β、IL-6、IL-10、MDA和SOD的水平。通过免疫荧光和蛋白质印迹法测定脑组织中核因子-E2 相关因子 2 (Nrf2) 和血红素加氧酶 1 (HO-1) 蛋白的表达。结果结果表明，天竺葵素能有效减少MCAO大鼠脑缺血体积，改善神经功能，从而提高记忆力和学习能力。随着TNF-α、TGF-β、IL-6和MDA的表达相应降低，IL-10和SOD水平升高，也促进了缺血性脑中Nrf2的核转移和HO-1的表达组织。结论 我们的数据表明，天竺葵素可改善 MCAO 大鼠的神经功能缺陷，其潜在的作用机制与 Nrf2/HO-1 信号通路的过表达有关。本研究将为治疗脑缺血/再灌注损伤提供一种新方法。