Ginsenoside Rg1 protects against sepsis-associated encephalopathy through beclin 1-independent autophagy in mice

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• 作者：Yinjiao Li ; MD^a ; ¹ ; Fang Wang ; MD^b ; ¹ ; Yan Luo ; MD ; PhD^a ; ^{ly11087@rjh.com.cn}
• 关键词：Ginsenoside Rg1 ; Sepsis-associated encephalopathy ; Cognitive impairment ; Inflammation ; Autophagy
• 刊名：Journal of Surgical Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：207
• 期：Complete
• 页码：181-189
• 全文大小：2713 K
• 卷排序：207

文摘

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.Materials and methodsSAE 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.ResultsRg1 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.ConclusionsThese 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.