Amelioration of concanavalin A-induced autoimmune hepatitis by magnesium isoglycyrrhizinate through inhibition of CD4(+)CD25(-)CD69(+) subset proliferation.
Amelioration of concanavalin A-induced autoimmune hepatitis by magnesium isoglycyrrhizinate through inhibition of CD4(+)CD25(-)CD69(+) subset proliferation.
复制标题
异甘草酸镁通过抑制 CD4( )CD25(-)CD69( ) 亚群增殖来改善刀豆球蛋白 A 诱导的自身免疫性肝炎。
DOI：
10.2147/dddt.s92440
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Wei H
中科院分区：
文献类型：
--
作者：
Yang Q;Wang J;Liu R;Wang Z;Li Y;Zhang Y;Hao X;Huang Y;Xie W;Wei H
异甘草酸镁（MGL）是甘草酸的一种新的立体异构体，临床上用作保肝药，其作用比甘草酸强，副作用少。本研究旨在探讨MGL对刀豆球蛋白A（ConA）诱导的自身免疫性肝炎的保护作用及其可能机制。在C57/6 J小鼠中，在给予或不给予MGL的情况下，通过Con A诱导肝炎;评价损伤评分和血清ALT。从脾细胞中分离CD 4 + T细胞，并在与MGL共培养后用Con A攻击。与单纯ConA攻击的小鼠相比，MGL处理的小鼠在ConA攻击12和24小时后的损伤评分显著改善。在血清ALT和AST水平中观察到相似的趋势。最有趣的结果是，在Con A激发12和24小时后，MGL给药显著降低了外周血单核细胞中CD 4 + CD 25 − CD 69 + T细胞的频率，而不是CD 4 + CD 25 + CD 69 + T细胞。此外，血清ALT水平与外周血单个核细胞中CD 4 + CD 25 − CD 69+细胞的频率显著相关，但与CD 4 + CD 25 + CD 69+细胞的相关性较弱。更重要的是，MGL（5 mg/mL）几乎完全消除了Con A激发后原代CD 4 + T细胞中CD 25 − CD 69+亚群的增殖。与单纯ConA攻击的小鼠相比，MGL给药组的NALP 3、NLRP 6和caspase-3表达显著降低，其中NALP 3和caspase-3以剂量依赖性方式下调。我们的研究结果表明，MGL可能有潜力作为一种治疗剂，在自身免疫性肝炎，改善肝损伤。其分子机制可能与抑制肝组织中CD 4 + CD 25 − CD 69+亚群增殖、下调炎性小体表达有关。
Magnesium isoglycyrrhizinate (MGL) is a new stereoisomer of glycyrrhizic acid, which is clinically used as a hepatoprotective medicine with more potent effects and less side effects than glycyrrhizic acid. This study was designed to evaluate the protective effects and possible mechanism of MGL against concanavalin A (Con A)-induced autoimmune hepatitis. Hepatitis was induced by Con A in C57/6J mice with or without MGL administration; injury score and serum ALT were evaluated. The CD4+ T-cells were isolated from splenocytes and challenged with Con A after coculturing with MGL. The injury score was significantly improved in MGL-treated mice after Con A challenging for 12 and 24 hours compared with those merely challenged with Con A. Similar trends were observed in the serum levels of ALT and AST. The most interesting result was that MGL administration significantly decreased the frequency of CD4+CD25−CD69+ T-cells rather than CD4+CD25+CD69+ T-cells in peripheral blood mononuclear cells, after Con A challenging 12 and 24 hours. Moreover, the serum ALT levels were markedly correlated with the frequency of CD4+CD25−CD69+ cells, but only weakly correlated with CD4+CD25+CD69+ cells in peripheral blood mononuclear cells. More importantly, MGL (5 mg/mL) almost completely eliminated the proliferation of the CD25−CD69+ subset in primary CD4+ T-cells after Con A challenge. Compared with merely Con A-challenged mice, those with MGL administration significantly demonstrated decreased NALP3, NLRP6, and caspase-3 expression, in which the NALP3 and caspase-3 downregulated in a dose-dependent manner. Our results indicate that MGL may have potential as a therapeutic agent in autoimmune hepatitis by ameliorating liver injury. Its molecular mechanism may be involved in inhibiting CD4+CD25−CD69+ subset proliferation and downregulating inflammasome expression in liver tissue.