摘要
目的研究刺五加皂苷对小鼠急性酒精性肝氧化损伤的保护作用及分子机制。方法采用Balb/c雄性小鼠随机分为对照组、酒精肝损伤模型组和3个不同剂量刺五加皂苷保护组。刺五加皂苷保护组每日给予低、中、高剂量皂苷灌胃连续1周。在第5~7日,模型组及各给药组动物给予无水乙醇(5 g·kg-1体重)灌胃。处死实验动物取血清检测谷丙转氨酶(ALT)和谷草转氨酶(AST),取肝组织检测丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)以及还原型谷胱甘肽(GSH),提取肝组织蛋白检测p38丝裂原活化蛋白激酶(p38MAPK)信号通路及核转录因子kappa B(NF-κB)通路及炎症因子肿瘤坏死因子-α(TNF-α)、白介素1β(IL-1β)和白介素6(IL-6)的表达。结果酒精性肝损伤能够显著提高动物血清中ALT和AST水平,同时显著提高氧化损伤产物MDA水平,降低抗氧化酶SOD、CAT和GSH水平,提高p38MAPK的磷酸化水平,促进NF-κB核转位,提高炎症因子TNF-α、IL-1β和IL-6的表达。而刺五加皂苷能够剂量依赖地改善上述酒精引起的各项指标变化。结论酒精引起明显的肝脏氧化损伤,刺五加皂苷能够通过提高抗氧化酶,降低氧化应激,抑制氧化还原调控的p38MAPK和NF-κB信号通路,抑制炎症因子释放,从而发挥抗酒精性肝氧化损伤的保护作用。
Objective To determine the protection mechanism of Aacanthopanax senticosus saponin for alcoholic liver oxidative injury in mice. Methods The mice were divided into a control group, an alcoholic model group and 3 Aacanthopanax senticosus saponin protection groups. The mice in the protection groups were given different dosages ofAacanthopanax senticosus saponins everyday. All mice except those in the control group were given ethanol (5 g·kg - 1) for 3 days from Day 5. The ALT and AST were determined by an automatic biochemical analyzer. The content of MDA and GSH, and the activities of SOD and CAT were determined by kits respectively. The protein levels of p38MAPK pathway and NF-κB pathway (p65) as well as the TNF-α, IL-1β and IL-6 were assayed by Western blot. Results The levels of ALT and AST were increased greatly by alcohol. At the same time, the MDA content was increasd as the levels of GSH, SOD and CAT decreased. After the alcohol treatment, p38MAPK and NF-κB pathways were activated with the increased expressions of TNF-α, IL-lβ and IL-6. Aacanthopanax senticosus saponin inhibited all of the changes above in a dose-dependent way. Conclusion Aacanthopanax senticosus saponin showed significant protection against alcoholic liver oxidative injury in mice. Aacanthopanax senticosus saponin may protect by elevating the antioxidant system to attenuate oxidative stress induced p38MAPK and NF-κB pathways activation, thus attenuating the expression of pro-inflammatory cytokines TNF-α, IL-1β and IL-6.
作者
岳斌
徐丽
李影娜
YUE Binl;XU Li;LI Ying-na(Department of Endocrinology,Staff Hospital of Changqing Oilfield,Xi'an 710018;Department of Geriatrics,Xi'an No.3 Hospital,Xi'an 710082)
出处
《中南药学》
CAS
2018年第9期1221-1224,共4页
Central South Pharmacy
基金
陕西省科技研发计划(No.2018SF-014)
关键词
活性氧
氧化应激
酒精性肝损伤
抗氧化剂
炎症
reactive oxygen species
oxidative stress
alcoholic liver injury
antioxidant
inflammation