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异甘草酸镁对刀豆蛋白A诱导的急性肝衰竭小鼠模型的影响
Effect of magnesium isoglycyrrhizinate on concanavalin A-induced acute liver failure in mice
文章发布日期:2020年06月08日  来源:  作者:高钰迪,田原,张向颖,等  点击次数:280次  下载次数:31次

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【摘要】:目的 研究异甘草酸镁(MgIG)对刀豆蛋白A(ConA)诱导的急性肝衰竭小鼠模型的作用及机制。方法 选取健康BALB/C小鼠90只,随机分为4组,分别为对照组、MgIG对照组,每组各10只;ConA模型组、MgIG+ConA预处理组,每组各35只(其中15只用来计算总生存率)。提取小鼠肝脏及外周血,测定生存率、血清转氨酶水平,肝组织HE染色评价小鼠肝损伤程度,TUNEL荧光染色及caspase-3蛋白活性检测评价小鼠肝细胞凋亡水平,液相芯片法检测小鼠血清炎症细胞因子IL-1β和TNFα含量。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果 ConA模型组小鼠总生存率为40%,MgIG+ConA预处理组小鼠总生存率为80%。ConA模型组血清ALT与AST水平较对照组均显著上升(P值均<0.01),MgIG+ConA预处理组血清ALT与AST水平较ConA模型组均显著降低(P值均<0.01)。对照组、MgIG对照组、ConA模型组及MgIG+ConA预处理组病理评分分别为1.0±0.2、1.2±0.3、3.7±0.6、2.3±0.5,组间比较差异有统计学意义(F=2.7,P<0.05);凋亡细胞/100细胞数值分别为0.2± 0.1、0.1±0.1、7.8±1.3、2.2±0.4,组间比较差异有统计学意义(F=27.6,P<0.001);caspase-3活性分别为0.813 ± 0.022、0.930 ± 0.033、1.347 ± 0.042、1.060±0.053,组间比较差异有统计学意义(F=51.072,P<0.001)。ConA模型组与对照组比较,血清IL-1β与TNFα水平均显著上升(P值均<0.05)。MgIG+ConA预处理组与ConA模型组比较,血清IL-1β与TNFα均显著下降(P值均<0.05)。结论 异甘草酸镁对刀豆蛋白A诱导的小鼠急性肝衰竭具有明显保护作用,减少肝细胞凋亡并减轻IL-1β和TNFα引起的肝脏炎症反应可能是其缓解肝损伤的机制。
【Abstract】:Objective To investigate the effect of magnesium isoglycyrrhizinate (MgIG) on concanavalin A (ConA)-induced acute liver failure in mice and its mechanism. Methods A total of 60 healthy BALB/C mice were randomly divided into control group with 10 mice, MgIG control group with 10 mice, ConA model group with 20 mice, and MgIG-ConA pretreatment group with 20 mice. The liver and peripheral blood were collected to evaluate survival rate, serum levels of aminotransferases, and degree of liver injury by HE staining of liver tissue; TUNEL fluorescence staining and activity of caspase-3 protein were used to evaluate the apoptosis of hepatocytes; the liquid chip method was used to measure the serum levels of the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results The overall survival rate of mice was 40% in the ConA model group and 80% in the MgIG-ConA pretreatment group. The ConA model group had significantly increased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with the control group(both P<0.01), while the MgIG+ConA pretreatment group had significantly reduced serum levels of ALT and AST compared with the ConA model group(both P<0.01). The control group, the MgIG control group, the ConA model group, and the MgIG-ConA pretreatment group had a pathological score of 1.0±0.2, 1.2±0.3, 3.7±0.6, and 2.3±0.5, respectively, and there was a significant difference between groups (F=2.7, P<0.05); the apoptotic cells/100 cells ratio was 0.2±0.1, 0.1±0.1, 7.8±1.3, and 2.2±0.4, respectively, in these four groups, and there was a significant difference between groups (F=27.6, P<0.001); the activity of caspase-3 protein was 0.813±0.022, 0.930±0.033, 1.347±0.042, and 1.060±0.053, respectively, in these four groups, and there was a significant difference between groups (F=51.072, P<0.001). Compared with the control group, the ConA model group had significant increases in serum levels of IL-1β and TNFα (both P<0.05); compared with the ConA model group, the MgIG+ConA pretreatment group had significant reductions in serum levels of IL-1β and TNFα(both P<0.05). Conclusion MgIG exerts a marked protective effect against ConA-induced acute liver failure in mice and can alleviate liver injury possibly by reducing hepatocyte apoptosis and alleviating liver inflammatory response caused by IL-1β and TNFα.
【关键字】:肝功能衰竭,急性; 甘草酸; 小鼠,近交BALB C
【Key words】:liver failure,acute; glycyrrhizic acid; mice,inbred BALB C
【引证本文】:GAO YD, TIAN Y, ZHANG XY, et al. Effect of magnesium isoglycyrrhizinate on concanavalin A-induced acute liver failure in mice[J]. J Clin Hepatol, 2020, 36(7): 1571-1576. (in Chinese)
高钰迪, 田原, 张向颖, 等. 异甘草酸镁对刀豆蛋白A诱导的急性肝衰竭小鼠模型的影响[J]. 临床肝胆病杂志, 2020, 36(7): 1571-1576.

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