Zhu Yufeng, Li Jinhang, Dai Lijun, Feng Wei
Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.
Department of Hemodialysis Room, Shidong Hospital of Yangpu District, Shanghai, 200082, China.
Cell Biochem Biophys. 2025 Mar;83(1):587-597. doi: 10.1007/s12013-024-01488-2. Epub 2024 Aug 26.
Sepsis patients are highly prone to sepsis-associated encephalopathy (SAE) complications, resulting in a high mortality rate. Recently, there has been no specific treatment for long-term improvement of cerebral function. Ginsenoside Rh2 is a form of steroidal saponins isolated from plant ginseng and has been shown to possess anti-inflammatory as well as neuroprotective characteristics; yet, the effect of ginsenoside Rh2 on SAE treatment is obscure. Accordingly, we proposed to investigate the effect of ginsenoside Rh2 in alleviating SAE damage. We established and utilized the SAE mouse model to determine the effect of Rh2 treatment on alleviating SAE. We determined the expression levels of Heme oxygenase-1(HO-1) and Nuclear factor erythroid 2-related factor 2 (Nrf2) as well as measured neural apoptosis by flow cytometry. Also, we quantified the levels of caspase-3, malondialdehyde (MDA), GSH-Px superoxide dismutase (SOD) and evaluated the animals' neural reflex function. First, used Rh2 to treat microglia BV2 and mouse neuron MN-c whether LPS exist or not, and then measured expression level of Iba-1, apoptotic rate, and ROS content applying flow cytometry. Also, we quantified the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). In comparison with the Sham group, the SAE model exhibited an elevated MDA content, caspase-3 activity, and cell apoptosis. On the other hand, the GSH-Px activity and SOD level were decreased along with a decreased neural reflex score. Our investigation concluded that Rh2 treatment significantly alleviated SAE damage and inhibited LPS-induced response via up-regulation of the Nrf2/HO-1 pathway to promote anti-oxidative stress capacity and inhibit neural cell apoptosis.
脓毒症患者极易发生脓毒症相关脑病（SAE）并发症，导致死亡率很高。最近，对于脑功能的长期改善尚无特异性治疗方法。人参皂苷Rh2是从植物人参中分离出的一种甾体皂苷，已显示具有抗炎和神经保护特性；然而，人参皂苷Rh2对SAE治疗的效果尚不清楚。因此，我们建议研究人参皂苷Rh2在减轻SAE损伤方面的作用。我们建立并利用SAE小鼠模型来确定Rh2治疗对减轻SAE的作用。我们测定了血红素加氧酶-1（HO-1）和核因子红细胞2相关因子2（Nrf2）的表达水平，并通过流式细胞术检测神经细胞凋亡情况。此外，我们对半胱天冬酶-3、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）、超氧化物歧化酶（SOD）的水平进行了定量，并评估了动物的神经反射功能。首先，无论是否存在脂多糖（LPS），均用人参皂苷Rh2处理小胶质细胞BV2和小鼠神经元MN-c，然后通过流式细胞术检测离子钙接头蛋白1（Iba-1）的表达水平、凋亡率和活性氧（ROS）含量。此外，我们对肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的水平进行了定量。与假手术组相比，SAE模型的MDA含量、半胱天冬酶-3活性和细胞凋亡率升高。另一方面，GSH-Px活性和SOD水平降低，同时神经反射评分降低。我们的研究得出结论，Rh2治疗可通过上调Nrf2/HO-1途径显著减轻SAE损伤并抑制LPS诱导的反应，从而提高抗氧化应激能力并抑制神经细胞凋亡。
