【摘要】 目的 探讨异甘草酸镁（magnesium isoglycyrrhizinate,MgIG）在刀豆蛋白A(concanavalin A,Con A)诱导的小鼠急性肝损伤中的作用及机制。方法 按照简单随机分组法将20只无特定病原体（specific pathogen free,SPF）级Balb/c小鼠分为正常对照组（4只）、MgIG组（4只）、Con A组（6只）、Con A+MgIG干预组（6只）。小鼠Con A(25 mg/kg)尾静脉注射12 h，构建急性肝损伤模型，干预组提前1 h给予MgIG(30 mg/kg)腹腔注射。检测丙氨酸氨基转移酶（alanine aminotransferase,ALT）和天门冬氨酸转氨酶（aspartate aminotransferase,AST）水平、白细胞介素（interleukin,IL）-1β、IL-6、肿瘤坏死因子（tumor necrosis factor α,TNF-α）、干扰素诱生蛋白10(interferon-inducibleprotein-10,IP-10)水平，检测IL-6、IL-1β、TNF-α、IP-10的mRNA相对表达量。体外实验中小鼠腹腔单核巨噬细胞用脂多糖（lipopolysaccharide,LPS,200 ng/ml）分别处理30 min、1 h、2 h和4 h，干预组小鼠腹腔单核巨噬细胞用MgIG(25μg/ml)预处理1h，检测IL-6、IL-β、TNF-α、IP-10炎症因子及磷酸化-p38丝裂原活化蛋白激酶（phospho-p38 mitogen activited protein kinase, p-p38）、磷酸化-cJun氨基末端激酶（phospho-c-JunN-terminalkinases,p-JNK）、磷酸化-细胞外调节蛋白激酶（phospho-extracellular regulated protein kinases,p-Erk）蛋白表达。结果 与Con A组相比，Con A+MgIG干预病理切片炎性细胞浸润明显减少，血清炎症因子[IL-6:(10695.71±4861.94)pg/ml vs (27650.88±5701.79)pg/ml;IL-1β:(13.37±8.18)pg/ml vs (56.55±9.29)pg/ml;IP-10:(3298.43±534.95)pg/ml vs (7413.38±1497.78)pg/ml;TNF-α(63.27±13.97)pg/ml vs (97.06±21.26)pg/ml]及mRNA相对表达量（IL-6:5.23±1.63 vs 16.06±4.55;IL-1β:0.88±0.45 vs 5.44±0.94;IP-10:126.24±29.54vs 454.40±114.81;TNF-α:9.55±2.75 vs 16.46±3.98）均显著降低（P均<0.05）。体外实验表明，与LPS诱导的模型组相比，MgIG干预组p-p38、p-Jnk、p-Erk蛋白水平明显降低，同时炎症因子mRNA相对表达量（IL-6:3627.91±1491.16 vs 6630.40±1149.59;IL-1β:259.92±49.47 vs 658.06±95.06;IP-10:4088.38±790.20 vs 7762.08±1007.42;TNF-α:117.09±15.29 vs 194.56±25.14）也显著降低（P均<0.05）。结论MgIG通过MAPK信号转导通路降低炎症反应显著改善Con A诱导的小鼠急性肝损伤，为MgIG在改善肝损伤的功能提供了理论支持。更多还原

【Abstract】 Objective To investigate the role and mechanism of magnesium isoglycyrrhizinate(MgIG) in concanavalin A(Con A)-induced acute liver injury. Methods In vivo experiments,20 specific pathogen free(SPF) Balb/c mice were randomly divided into normal control group(4 cases), MgIG control group(4 cases), Con A model group(6 cases) and Con A + MgIG intervention group(6 cases) by simple randomization grouping method. The mice were injected with Con A(25 mg/kg) intravenously into the tail vein for 12 h to establish an acute liver injury model, and the intervention mice were injected with MgIG(30 mg/kg) intraperitoneally 1 h earlier. Levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST),interleukin(IL)-1β, IL-6, tumor necrosis factor α(TNF-α) and interferon-inducible protein-10(IP-10) were detected. The relative mRNA expression levels of IL-6, IL-1 β, TNF-α and IP-10were also detected. For in vitro experiments, the mice peritoneal mononuclear macrophages were treated with lipopolysaccharide(LPS, 200 ng/ml) for 30 min, 1 h, 2 h and 4 h, and the mice peritoneal mononuclear macrophages in the intervention group were pretreated with MgIG(25 μg/ml) for 1 h, and the expression of inflammatory factors(IL-6, IL-β, TNF-α, IP-10) and related proteins [phospho-p38 mitogen activited protein kinase(p-p38), phosphoc-JunN-terminal kinases(p-JNK), phospho-extracellular regulated protein kinases(p-Erk)]were detected. Results Compared with those in Con A model group, the inflammatory cell infiltration of mice in Con A + MgIG intervention group reduced significantly, serum inflammatory factors [IL-6:(10695.71 ± 4861.94) pg/ml vs(27650.88 ± 5701.79) pg/ml;IL-1β:(13.37 ± 8.18) pg/ml vs(56.55 ± 9.29) pg/ml; IP-10:(3298.43 ± 534.95) pg/ml vs(7413.38 ± 1497.78) pg/ml; TNF-α(63.27 ± 13.97) pg/ml vs(97.06 ± 21.26) pg/ml] and relative m RNA expression levels(IL-6: 5.23 ± 1.63 vs 16.06 ± 4.55; IL-1β: 0.88 ± 0.45 vs 5.44 ± 0.94;IP-10: 126.24 ± 29.54 vs 454.40 ± 114.81; TNF-α: 9.55 ± 2.75 vs 16.46 ± 3.98) also reduced significantly(all P < 0.05). Results of in vitro experiments showed that compared with those in LPS model group, the levels of p-p38, p-Jnk and p-Erk proteins in the MgIG intervention group reduced significantly, the relative mRNA expression levels of inflammatory factor genes(IL-6: 3627.91 ± 1491.16 vs 6630.40 ± 1149.59; IL-1β: 259.92 ± 49.47 vs 658.06 ± 95.06;IP-10: 4088.38 ± 790.20 vs 7762.08 ± 1007.42; TNF-α: 117.09 ± 15.29 vs 194.56 ± 25.14)also reduced significantly(all P < 0.05). Conclusions MgIG can remarkably ameliorate Con A-induced acute liver injury in mice by reducing the inflammatory response through MAPK signaling transduction pathway, which provided theoretical support for the ability of MgIG to recover liver injury in clinic.更多还原