甲基莲心碱减轻D-半乳糖胺/脂多糖诱导的小鼠急性肝损伤作用研究

doi:10.3969/j.issn.1672-5069.2018.04.015

摘要/Abstract

摘要： 目的研究甲基莲心碱对D-半乳糖胺/脂多糖诱导的小鼠急性肝损伤的保护作用。方法将80只小鼠随机分为4组（n=20）,在正常组和模型组小鼠给予生理盐水灌胃,而在另两实验组则分别给予小剂量（100 mg.kg^-1）和大剂量（300 mg.kg^-1）甲基莲心碱灌胃。然后在实验组给予D-半乳糖胺/脂多糖诱导制备急性肝损伤模型。每组选择10只小鼠取血,分别检测血清ALT、AST、SOD、MDA、GSH、TNF-α、IL-6和IL-10水平,并取肝组织,行病理学检查,另10只小鼠用于观察存活期。结果模型组小鼠血清ALT和AST水平分别为（272.4±42.8） U/L和（497.2±62.1） U/L,甲基莲心碱处理组小鼠血清ALT和AST水平均显著降低,差异有统计学意义（P<0.05）,而以大剂量甲基莲心碱处理组为明显;模型组小鼠血清SOD和GSH水平分别为（37.5±6.2） U/mL和（11.8±2.7）μmol/L,血清MDA水平为（9.2±1.4） mol/L,甲基莲心碱处理组小鼠血清SOD和GSH水平显著高于模型组,而血清MDA水平显著低于模型组（P<0.05）;模型组小鼠血清TNF-α、IL-6和IL-10水平分别为（587.6±48.9） pg/ml、（153.4±18.0）pg/ml和（96.4±9.7）pg/ml,甲基莲心碱处理组小鼠血清TNF-α和IL-6水平显著降低,血清IL-10水平显著升高（P<0.05）,而大剂量甲基莲心碱处理组小鼠血清TNF-α、IL-6和IL-10水平与小剂量甲基莲心碱处理组比,差异无统计学意义（P>0.05）;模型组小鼠12 h存活率为60.0%,24 h存活率为10.0%,小剂量甲基连心碱处理组小鼠12 h存活率为80.0%,24 h存活率为50.0%,而大剂量甲基莲心碱处理组小鼠12 h存活率为90.0%,24 h存活率为70.0%,组间差异有统计学意义（P<0.05）。结论甲基莲心碱可缓解D-半乳糖胺/脂多糖诱导的小鼠急性肝损伤,其机制可能与抑制氧化应激反应有关。

关键词: 急性肝损伤, 甲基莲心碱, 氧化应激, D-半乳糖胺, 脂多糖, 小鼠

Abstract: Objective To study the protective effect of neferine on acute liver injury induced by D- GalN / LPS in mice. Methods 80 mice were randomly divided into four groups, 20 in each and the mice in normal control and model group, saline was given by gavage, and the mice in the other two experiment groups was given intragasticly neferine at low （100 mg.kg^-1）and large （300 mg.kg^-1） dose. At the end of the last administration, 10 mice in each group were sacrificed to obtain blood for serum ALT, AST, SOD, MDA, GSH, TNF-α, IL-6 and IL-10 detection, and another ten mice in each group were followed-up for survival observation. The hepatic pathological examination were also performed. Results Serum ALT and AST levels in the model group were（272.4±42.8） U/L and（497.2±62.1） U/L,respectively, while they significantly decreased in neferine-intervened groups （P<0.05）,especially in mice with large neferine intervention;serum SOD and GSH levels in the model were （37.5±6.2） U/ml and （11.8±2.7） μmol/L,serum MDA level was （9.2±1.4）mol/L, while serum SOD and GSH levels in neferine-intervened groups significantly increased and serum MDA level significantly decreased （P<0.05）;serum TNF-α,IL-6 and IL-10 levels in the model were （587.6±48.9）pg/ml, （153.4±18.0） pg/ml and （96.4±9.7）pg/ml,respectively,while serum TNF-α and IL-6 levels in neferine-intervened groups significantly decreased, and serum IL-10 level significantly increased（P<0.05）,without significant differences between the two neferine-intervend groups（P>0.05）; the 12 h and 24 h survival rates in the model were 60.0% and 10.0%,while they were 80.0% and 50.0% in low-dose neferine-intervened group, and 90.0% and 70.0% in large-dose neferine-intervened group （P<0.05）. Conclusion Neferine can alleviate acute liver injury induced by D- GalN / LPS administration in mice, and the mechanism might be related to the inhibition of oxidative stress.

Key words: Acute liver injury, Neferine, Oxidative stress, D- GalN, LPS, Mice

王念, 魏纯玲, 蒋世双, 陶武, 唐泽. 甲基莲心碱减轻D-半乳糖胺/脂多糖诱导的小鼠急性肝损伤作用研究[J]. 实用肝脏病杂志, 2018, 21(4): 545-548.

Wang Nian, Wei Chunling, Jiang Shishuang, et al. Protective effect of neferine on mice with D-GalN / LPS-induced acute liver injury by inhibiting oxidative stress[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2018, 21(4): 545-548.

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