摘要
目的探索紫草素对刀豆蛋白A(concanavalin A,Con A)诱导的急性肝损伤的保护作用及其可能机制.方法通过尾静脉注射Con A建立急性肝损伤模型.小鼠随机分为正常组、肝损伤模型组、紫草素低剂量组(12.5 mg/kg)、紫草素中剂量组(25 mg/kg)、紫草素高剂量组(50 mg/kg),共计5个分组.检测不同分组之间的谷丙转氨酶(alanine transaminase,ALT)、谷草转氨酶(aspartate transaminase,AST)水平;HE染色比较不同分组之间的病理改变;一氧化氮检测试剂盒检测不同分组之间的一氧化氮水平;Western blot测定一氧化氮合酶(inducible nitric oxide synthase,iNOS)、核因子-κB(nuclear factor-κB,NF-κB)、IκBα和IκBβ的表达.结果与正常组相比,模型组中血清中的ALT和AST水平显著升高(P<0.05);模型组肝组织坏死明显,坏死率差异具有统计学意义;模型组肝组织中NO的合成增多(P<0.05);模型组肝组织中iNOS和NF-κB表达增多,IκBα和IκBβ的表达减少.与模型组相比,紫草素(50 mg/kg)显著降低小鼠血清中的ALT和AST水平,并减少肝细胞坏死率;同时减少iNOS和NF-κB表达,IκBα和IκBβ的表达则增多.低剂量组(12.5 mg/kg)和中剂量组(25 mg/kg)与模型组比较无统计学差异.结论紫草素(50 mg/kg)可以显著改善Con A诱导的急性肝损伤,且可能是通过抑制NF-κB信号通路激活,进而减少NO合成来实现的.
AIM To investigate the effect of shikonin on concanavalin A(Con A)-induced acute liver injury in mice and explore the underlying mechanisms.METHODS Acute liver injury was induced by Con A in Balb/c mice through tail injection.The mice were randomly divided into five groups of fourteen mice as follows:(1) normal group;(2) Con A-induced model group;(3) lowdose(12.5 mg/kg) shikonin + Con A group;(4)medium-dose(25 mg/kg) shikonin + Con A group;(5) high-dose(50 mg/kg) shikonin + Con A group.Histological grading and the measurement of the levels of alanine transaminase(ALT),aspartate transaminase(AST),nitric oxide(NO),inducible nitric oxide synthase(iNOS),nuclear factor-κB(NF-κB),IκBα,and IκBβ were performed.RESULTS Compared to the normal group,the histological grade as well as the levels of ALT,AST,NO,iNOS and NF-κB significantly increased in the model group,but the levels of IκBα and IκBβ were decreased.After shikonin(50 mg/kg)treatment,the histological grade and the levels of ALT,AST,NO,iNOS and NF-κB significantly were decreased,and the levels of IκBα and IκBβ were increased.The doses of 12.5 mg/kg and 25 mg/kg worked inefficiently.CONCLUSION Shikonin(50 mg/kg) protects against Con A-induced liver injury by decreasing the level of NO,which may correlate with the amelioration of NF-κB activity.
出处
《世界华人消化杂志》
CAS
2016年第25期3689-3695,共7页
World Chinese Journal of Digestology