Li Yinjiao, Wang Fang, Luo Yan
Department of Anesthesiology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Department of Anesthesiology and Intensive Care, Changhai Hospital, Second Military Medical University, Shanghai, China.
J Surg Res. 2017 Jan;207:181-189. doi: 10.1016/j.jss.2016.08.080. Epub 2016 Aug 31.
Sepsis-associated encephalopathy (SAE), a commonly complicated syndrome, is associated with increased mortality in patients with sepsis. Currently, no specific diagnostic test or effective intervention exists to improve long-term consequences on cerebral function. Ginsenoside Rg1 (Rg1), a major component in ginseng, was reported to have pleiotropic properties including anti-inflammation and neuroprotection. The aim of our study was to investigate the protective effect of Rg1 on SAE and the potential mechanism.
SAE model was prepared by inducing cecal ligation and puncture (CLP) in mice. Rg1 was injected 1 h before the CLP operation. Survival rate within 7 d after operation was analyzed. Surviving mice were subjected to Morris water maze tests and the brains were collected for histopathologic evaluation and immunohistochemistry. The hippocampus was obtained for Western blot, real time polymerase chain reaction, and enzyme-linked immunosorbent assay analysis.
Rg1 improved the postoperative survival rate and protected against sepsis-associated learning and memory impairments (Morris water maze). Besides, Rg1 was able to attenuate brain histopathologic changes (hematoxylin and eosin staining), suppress Iba1 activation, decrease the expressions of inflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interleukin 6), and reduce neuronal apoptosis (cleaved caspase 3 activation) in hippocampus. Furthermore, the mechanism study showed that Rg1 suppressed the expressions of light chain 3-II and p62 in hippocampus but not beclin 1.
These findings suggested that Rg1 improved the survival rate and ameliorated cognitive impairments partially through regulating cerebral inflammation and apoptosis. In addition, the action mechanism might be noncanonical beclin 1-independent autophagy pathway. Rg1 may be a promising treatment strategy for SAE.
脓毒症相关脑病（SAE）是一种常见的并发症，与脓毒症患者死亡率增加相关。目前，尚无特异性诊断试验或有效干预措施可改善对脑功能的长期影响。人参皂苷Rg1（Rg1）是人参中的主要成分，据报道具有多种特性，包括抗炎和神经保护作用。本研究旨在探讨Rg1对SAE的保护作用及其潜在机制。
通过对小鼠进行盲肠结扎和穿刺（CLP）制备SAE模型。在CLP手术前1小时注射Rg1。分析术后7天内的生存率。对存活小鼠进行莫里斯水迷宫试验，并收集大脑进行组织病理学评估和免疫组织化学分析。获取海马进行蛋白质印迹、实时聚合酶链反应和酶联免疫吸附测定分析。
Rg1提高了术后生存率，并预防了脓毒症相关的学习和记忆障碍（莫里斯水迷宫）。此外，Rg1能够减轻脑组织病理学变化（苏木精和伊红染色），抑制Iba1激活，降低炎症细胞因子（肿瘤坏死因子α、白细胞介素1β和白细胞介素6）的表达，并减少海马神经元凋亡（裂解的半胱天冬酶3激活）。此外，机制研究表明，Rg1抑制海马中轻链3-II和p62的表达，但不抑制贝林1。
这些发现表明，Rg1通过调节脑炎症和细胞凋亡部分提高了生存率并改善了认知障碍。此外，作用机制可能是非经典的不依赖贝林1的自噬途径。Rg1可能是一种有前途的SAE治疗策略。
