Wu J, Chen X, Lin X, Li Z, Cao Z, Huang W, Shao D, Hussain S A, Pu K, Zhao N
Department of Neurosurgery, The First Hospital of Kunming (Affiliated Calmette Hospital of Kunming Medical University), Kunming, China.
Physiol Res. 2025 Apr 30;74(2):313-326.
Stroke and cerebral ischemia/reperfusion (IR) injury are severe conditions characterized by impaired blood flow to the brain, leading to tissue infarction and neurological impairments. Panax notoginseng saponins (PNS) have displayed various beneficial effects in alleviating cerebrovascular disorders. This study aimed to investigate the neuroprotective capacity of PNS in a rat model of middle cerebral artery occlusion (MCAO)-induced cerebral IR injury, focusing specifically on understanding the involvement of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in mediating this protective effect. Male Sprague-Dawley rats (n=45, weighing 250-280g and aged 12 weeks) were utilized in this experiment. Cerebral IR injury was induced by subjecting the rats to 30 minutes of MCAO followed by 24 hours of reperfusion. Prior to the surgery, PNS (120mg/kg) was administered once daily via gavage for 14 days. The evaluation measures included assessing cerebral infarct volume, neurological function using the Longa method, conducting histopathological analysis, examining the expression of SIRT1, Nrf2, and HO-1 genes and proteins, as well as measuring the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA). Pretreatment with PNS markedly decreased infarct volume, enhanced neurological function, and mitigated histopathological alterations. Additionally, PNS intake resulted in the upregulation of SIRT1, Nrf2, and HO-1 genes and proteins, boosted enzymatic antioxidant activity, and lowered MDA levels, pointing towards a diminution in oxidative stress. The multifaceted antioxidant and neuroprotective properties of PNS underscore its promising role in preserving neuronal function, mitigating oxidative damage, and promoting tissue survival in ischemic conditions. These benefits were associated with the modulation of the SIRT1/Nrf2/HO-1 signaling pathway, emphasizing the therapeutic significance of PNS in addressing cerebral IR injury and related neurological complications. Key words: Ischemia/reperfusion injury, Neuroprotection, Oxidative stress, Panax notoginseng saponins, Stroke.
中风和脑缺血/再灌注（IR）损伤是严重病症，其特征是脑部血流受损，导致组织梗死和神经功能障碍。三七总皂苷（PNS）在缓解脑血管疾病方面已显示出多种有益作用。本研究旨在探讨PNS在大脑中动脉闭塞（MCAO）诱导的脑IR损伤大鼠模型中的神经保护能力，特别关注了解沉默调节蛋白1（SIRT1）/核因子红细胞2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）通路在介导这种保护作用中的参与情况。本实验使用雄性Sprague-Dawley大鼠（n = 45，体重250 - 280g，年龄12周）。通过使大鼠进行30分钟的MCAO然后再灌注24小时来诱导脑IR损伤。在手术前，通过灌胃每天一次给予PNS（120mg/kg），持续14天。评估措施包括评估脑梗死体积、使用Longa法评估神经功能、进行组织病理学分析、检测SIRT1、Nrf2和HO-1基因及蛋白的表达，以及测量谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和丙二醛（MDA）的水平。PNS预处理显著降低了梗死体积，增强了神经功能，并减轻了组织病理学改变。此外，摄入PNS导致SIRT1、Nrf2和HO-1基因及蛋白上调，提高了酶抗氧化活性，并降低了MDA水平，表明氧化应激减轻。PNS的多方面抗氧化和神经保护特性强调了其在缺血条件下保护神经元功能、减轻氧化损伤和促进组织存活方面的潜在作用。这些益处与SIRT1/Nrf2/HO-1信号通路的调节有关，强调了PNS在治疗脑IR损伤和相关神经并发症方面的治疗意义。关键词：缺血/再灌注损伤；神经保护；氧化应激；三七总皂苷；中风
