人参皂苷Rg1通过糖皮质激素受体相关NF-κB信号通路发挥抗炎作用抵抗酒精性肝炎研究

Anti-inflammatory Function of Ginsenoside Rg1 on Alcoholic Hepatitis through Glucocorticoid Receptor Related Nuclear Factor-kappa B Pathway

目的人参皂苷Rg1是人参提取物中最具药理活性的皂苷之一。基于实验室前期研究及对肝炎的认识,本实验的目的在于研究Rg1在酒精诱导的小鼠肝炎模型中是否发挥抗炎作用,并探讨其可能机制。方法口服给予C57BL/6小鼠6 g/kg酒精,1 h后给予Rg1(10,20或40 mg/kg)或者阳性对照地塞米松(1 mg/kg)连续9 d。对血清进行生化分析、肝组织染色观察、免疫组化以及WB蛋白检测。结果与模型组比较,发现Rg1显著提高小鼠的生存率并降低异常升高的血清生化指标(P<0.05)。病理和超显微结构表明酒精性肝损伤后肝组织病变情况,而Rg1反转其病变。过度产生的炎症因子包括TNF-α、IL-1β及IL-6亦被Rg1抑制。Rg1通过影响糖皮质激素受体调节NF-κB使肝脏恢复到正常情况。结论 Rg1可能发挥配体作用促进糖皮质激素受体调节NF-κB进而对抗酒精性肝炎。

Objective Ginsenoside Rg1 is one of the most pharmacological active constituents from ginseng extract. Based on prior experimental results and the understanding of alcoholic hepatitis, the major aim of this study is to investigate whether Rg1 is beneficial in a rodent model mimic alcoholic hepatic injury associated with binge drinking and explore the underlying possible mechanisms. Methods C57BL/6 mice were given oral consumption of 6 g/kg alcohol 1 h after treated with Rg1（10,20 and 40 mg/kg） or dexamethasone（1 mg/kg） for 9 consecutive days. Blood were performed biochemical analyses and liver fragments were processed for microscopy, immunohistochemistry and western blot analysis. Results Compared with the model group, Rg1 treatment significantly reversed the high mortality rate induced by alcohol consumption and also alleviated liver impairment as evidenced by the decrease of serum parameters. Meanwhile, histological and ultrastructural analysis of alcoholic groups showed hepatocellular impairment but restored in Rg1-treated groups. Overproductive inflammatory cytokines including TNF-α, IL-1β and IL-6 were also suppressed by Rg1. Rg1 modulated liver to normal levels by adjusting the glucocorticoid receptor related NF-κB pathway Conclusion This study demonstrates that Rg1 might promote glucocorticoid receptor mediating the repression of NF-κB and inhibit the inflammatory reactions in alcoholic hepatitis.