注射用胡黄连总苷对ConA引起小鼠急性免疫性肝损伤的保护作用研究  

Protective Effect of Total Glucoside of Picrorhiza Scrophulariflora for Injection on Concanavalin A-induced Liver Injury in Mice

作　　者：王淑娟[1] 贾志丹 魏怀玲 苗露阳[3] 张丹[3] 孙华[3] 

机构地区：[1]长春工业大学,吉林长春130012 [2]国药一心制药有限公司,吉林长春130000 [3]中国医学科学院药物研究所,北京100050

出　　处：《中国药物警戒》2013年第12期705-708,共4页Chinese Journal of Pharmacovigilance

摘　　要：目的利用Concanavalin A(ConA)引起的免疫性肝损伤模型,对注射用胡黄连总苷的保肝活性和量效关系进行研究。方法注射用胡黄连总苷静脉给予ICR小鼠(0.5~8mg·kg-1×5),于末次给药后2h,动物尾静脉ConA 20mg·kg-1,建立急性免疫性肝损伤模型,16h后处理动物,制备血清,全自动生化分析仪检测血清ALT,AST及LDH水平,H.E.染色考察肝脏病理状态。结果 ConA 20mg·kg-1能引起小鼠显著的急性免疫性肝损伤,血清ALT,AST及LDH含量均显著升高,肝组织出现以炎症细胞浸润、肝细胞坏死为主要特征的病理改变。注射用胡黄连总苷0.5~4mg·kg-1剂量对ConA引起的肝损伤有显著保护作用,明显降低血清转氨酶水平,改善肝脏病理状态,其中1mg·kg-1剂量药效最佳,8mg·kg-1剂量药效有所下降,但此剂量未显示明显毒性。结论注射用胡黄连总苷对ConA引起的免疫性肝损伤有明确的保护作用,其起效剂量低,高于8mg·kg-1活性下降,在临床实验时需注意剂量的选择问题。Objective To study the protective effect of total glucoside o^Picrorhiza scrophulariflora（TGP） for infection on Concanavalin A（ConA）-induced acute liver injury in ICR mice. Methods ICR mice were given intravenously TGP injection 0.5- 8mg·kg-1 for five days（one time/day）. After the last administration 2h, the mice were injected intravenously ConA 20mg·kg-1 to establish the immunological liver damage model. All animals were killed on 16h atier ConA treatment. The activities of ALT, AST and LDH were measured by automatic chemistry analyzer（TBA-40FR）. Liver histopathological changes were examined by H.E. and light microscopy. Results ConA 20mg＇kg-1 could induced significant liver damage, expressed in the higher serum ALT,AST,LDH activities and the apoptosis or inflammatory cell infiltration in liver tissue. TGP injection 0.5 - 4mg·kg-1 showed significantly protective effect to hver damage induced by ConA, which could reduce serum transarninase activities and prevent the pathological injury. The optimum dose is lmg·kg-1. There was a reduced efficacy when the dose is 8mg·kg-1. While at this dose, there are no obvious toxicity. Conclusion TGP injection showed a significant protective effect on Con_A-induced liver injury in mice. Its effective dose is low and the therapeutic activity will cut down when the dose is higher than 8mg·kg-1. It should be carefi.fl to the dose choice in clinical trial.

关 键 词：胡黄连 总苷 注射液 CONA 肝损伤 

分 类 号：R286[医药卫生—中药学] R285.5[医药卫生—中医学]