丹参总酚酸对刀豆蛋白A所致小鼠急性肝损伤的保护作用及机制

摘要

Objective To investigate the protective effect of salvianolic acids on acute liver injury caused by con-canavalin A (ConA) in mice and its mechanism.Methods Male C57BL/6 (B6) mice were randomly divided into four groups:the normal control group, which received saline only; salvianolic acids-treated group, which received salvianolic acids only;ConA-treated group, which was administered with ConA (40 mg/kg) via tail vein injection;and the salvianolic acids+ConA-treated group, which received salvianolic acids at a dose of 50 mg/kg 30 min prior to ConA injection.After 16-hour intervention, the liver function was analyzed by fully automatic biochemical analyser, pathologic changes were ob-served by HE staining, and the relevant inflammatory mediators ( extracellular histones, IL-1 , IL-6, IL-18 and TNF-α) were evaluated by ELISA and Luminex.Results The administration of ConA to mice caused severe liver injury, as evi-denced by significantly increased ALT and AST levels, necrosis and apoptosis of liver cells and inflammatory cell infiltra-tion.Compared with the ConA-treated mice, salvianolic acids plus ConA-treated mice showed a significantly decreasing trend of ALT, AST, as well as the reduced liver injury.Besides, the concentrations of extracellular histones, IL-1 , IL-6, IL-18 and TNF-αwere significantly decreased in the ConA-treated group as compared with those of the normal control group and salvianolic acids-treated group (all P<0.05).Compared with the ConA-treated group, all indexes of the salvianolic acids+ConA-treated group were decreased (all P<0.01), but were higher than those of the normal control group and salvianolic acids-treated group (all P<0.01).Conclusion Salvianolic acids have significant protective effect on ConA-in-duced liver injury in mice, likely due to its ability of decreasing the levels of extracellular histones and various cytokines.%目的：研究丹参总酚酸对刀豆蛋白A（ ConA）所致急性肝损伤小鼠的保护作用及机制。方法将野生型C57BL／6（ B6）雄性小鼠随机分为正常对照组、丹参总酚酸组、ConA组和丹参总酚酸＋ConA组。 ConA组小鼠通过尾静脉注射ConA（40 mg／kg）诱导肝损伤；丹参总酚酸＋ConA组小鼠先经腹腔注射丹参总酚酸溶液（50 mg／kg），30 min后再给予相同剂量的ConA；正常对照组仅尾静脉注射生理盐水，丹参总酚酸组仅腹腔注射丹参总酚酸溶液，剂量同上。干预16 h后，采用全自动生化分析仪测肝功能，应用HE染色观察肝脏病理学变化，应用ELISA和Luminex方法检测细胞外组蛋白及相关炎症分子（ IL-1、IL-6、IL-18、TNF-α）的水平。结果小鼠尾静脉注射Co-nA后发生了明显的肝损伤，表现为血浆ALT、AST水平显著升高，大量肝细胞凋亡坏死和炎症细胞浸润；给予丹参总酚酸干预能显著减轻小鼠肝损伤，降低ALT、AST水平。与正常对照组或丹参总酚酸组相比，ConA组的细胞外组蛋白、IL-1、IL-6、IL-18和TNF-α水平均升高（P均＜0．01）；与ConA组比较，丹参总酚酸＋ConA组小鼠各指标均降低（P均＜0．01），但仍高于正常对照组或丹参总酚酸组（P均＜0．01）。结论丹参总酚酸对ConA所致的小鼠急性肝损伤有显著保护作用，其机制可能与降低细胞外组蛋白和相关的细胞因子水平有关。