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

Protective effect of salvianolic acids on acute liver injury caused by concanavalin A in mice

目的研究丹参总酚酸对刀豆蛋白A(Con A)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、Con A组和丹参总酚酸+Con A组。Con A组小鼠通过尾静脉注射Con A(40 mg/kg)诱导肝损伤;丹参总酚酸+Con A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Con A;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Con A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,Con A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Con A组比较,丹参总酚酸+Con A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Con A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。

Objective To investigate the protective effect of salvianolic acids on acute liver injury caused by concanavalin A（ Con A） in mice and its mechanism. Methods Male C57 BL /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; Con A-treated group,which was administered with Con A（ 40 mg / kg） via tail vein injection; and the salvianolic acids ＋ Con A-treated group,which received salvianolic acids at a dose of 50 mg / kg 30 min prior to Con A injection. After16-hour intervention,the liver function was analyzed by fully automatic biochemical analyser,pathologic changes were observed 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 Con A to mice caused severe liver injury,as evidenced by significantly increased ALT and AST levels,necrosis and apoptosis of liver cells and inflammatory cell infiltration. Compared with the Con A-treated mice,salvianolic acids plus Con A-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-α were significantly decreased in the Con A-treated group as compared with those of the normal control group and salvianolic acids-treated group（ all P〈0. 05）. Compared with the Con A-treated group,all indexes of the salvianolic acids ＋ Con A-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 Con A-induced liver injury in mice,likely due to its ability of decreasing the levels of extracellular histones and various cytokines.