Aim To investigate the effect of Aesculus hippocastanum seed extract(AH) on concanavalin A (ConA)-induced acute liver injury in mice,and to ex-plore whether the mechanism was related to the inhibi-tory effect of AH on oxidative stress and c-Jun N-termi-nal kinase (JNK). Methods ConA(20 mg·kg-1) was administered via tail vein injecting to induce he-patic damage in mice. The groups of AH were given at 12.5,25,50 mg·kg-1by oral gavage separately for 20 days. The serum levels of AST,ALT,TP,and Alb were determined by automatic biochemical analyzer and the A/G ratio was calculated. TNF-α and IFN-γ levels were assayed by ELISA. The liver tissue was attained by HE and the histopathological changes were calculat-ed. The MDA, SOD, GSH contents of liver tissues were assayed by related kits. The activity of caspase-3 was detected by spectrophotometry. The expressions of cytochrome C and Bax, Bcl-2, p-JNK and p-Akt were detected by Western blot. Results The serum levels of ALT, AST, IFN-γ and TNF-α in AH groups were significantly lower than those in ConA-injured group, while the levels of TP,Alb and A/G were significantly higher. The SOD and GSH levels of liver tissues signif-icantly increased and MDA level decreased; liver his-topathological changes were consistent with those of the serological indicators, and AH treatment significantly reduced the pathological damage induced by ConA. In AH group,the expression of cytochrome C,caspase-3, Bax/Bcl-2 ratio and p-JNK markedly decreased, while the expression of p-Akt protein increased compared with ConA model group. Conclusion AH could sig-nificantly protect the ConA-induced acute liver injury in mice via inhibition of ROS and JNK pathway.%目的 观察马栗种子提取物(AH)对刀豆蛋白A(Co-nA)诱导的小鼠急性肝损伤的保护作用,并探讨其相关机制是否与AH抑制氧化应激及其介导的 c-Jun氨基末端激酶(JNK)途径有关.方法 小鼠尾静脉一次性注射ConA(20 mg·kg-1)制备急性肝损伤模型,AH保护组分别给予12.5、25、50 mg·kg-1AH连续灌胃20 d预保护;全自动生化分析仪检测血清ALT、AST、TP、Alb、A/G;ELISA法检测小鼠血清IFN-γ、TNF-α水平;肝组织HE染色并进行病理学损伤分级评估;试剂盒检测肝组织MDA、SOD、GSH水平;分光光度法检测caspase-3活性;Western blot 检测caspase-3、Bax、Bcl-2、p-JNK、p-Akt的蛋白表达情况.结果 与 ConA 模型组相比,不同浓度的AH处理组小鼠血清ALT、AST、IFN-γ、TNF-α水平明显降低,TP、Alb、A/G比明显增高;肝组织的MDA水平明显降低,SOD、GSH水平明显升高.肝组织病理学与血清学指标改变相一致,AH处理组相比ConA模型组病理损伤明显减轻,病理损伤分级降低;与模型组相比,AH保护组细胞色素 C、caspase-3、Bax/Bcl-2、p-JNK均明显降低,而 p-Akt蛋白表达升高.结论 AH可明显改善ConA诱导的小鼠急性肝损伤,其机制与AH抗氧化应激,进而抑制JNK/线粒体凋亡途径有关.
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