苯丙氨酸二肽类化合物Y101对刀豆蛋白A致小鼠免疫性肝损伤的保护作用  

Protective effects of phenylalanine dipeptide compounds Y101 on liver injury induced by CnoA in mice

作　　者：于珊[1,2] 徐雪钰[3] 梁光义[2] 黄正明[1] 

机构地区：[1]解放军第302医院药学部临床药理研究室,北京100039 [2]贵阳中医学院中药药理教研室,贵阳550002 [3]解放军第309医院药剂科,北京100091

出　　处：《中国新药杂志》2012年第1期78-81,87,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30760292);国家科技部“国际合作”新药基金(2008DFB30110);973计划前期研究专项(2007CB516800);贵州省中药现代化项目(黔科合农字[2006]5001号)

摘　　要：目的:观察苯丙氨酸二肽类化合物Y101(简称Y101)对刀豆蛋白A(CnoA)致小鼠免疫性肝损伤的保护作用,并探讨其可能的作用机制。方法:将昆明种小鼠随机分为生理盐水组、CnoA模型组、Y101低、中、高(25,50,100 mg.kg-1)剂量组和联苯双酯组(LB,150 mg.kg-1)。除生理盐水组外,CnoA模型组和各给药组均于d 5和d 7给药1 h后尾静脉注射20 mg.kg-1 CnoA溶液使之中毒(按0.1 mL/10 g体重)。末次中毒后禁食不禁水,8 h后眼球取血,并迅速取肝脏备检。检测其血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)含量。取肝脏,称重,检测肝脏中丙二醛(MDA)、一氧化氮(NO)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)的含量;另取肝脏做病理组织学检查。结果:与正常组比较,模型组小鼠血清中ALT、AST活性,肝内MDA、NO含量及肝脾指数显著升高(P<0.01),肝内SOD、GSH水平及胸腺指数明显降低(P<0.01)。低、中、高剂量Y101对肝损伤大鼠上述指标均有不同程度的改变,且呈良好的剂量关系。给予Y101治疗后,中、高剂量组的肝组织病理变化均明显轻于模型组。结论:Y101对CnoA致小鼠免疫性肝损伤具有保护作用,其作用机制可能与其抗氧化作用有关。Objective：To observe the protective effect of phenylalanine dipeplicle compounds YIO1 on immune liver injury mouse induced by CnoA and investigate the probable meehanism. Methods： The mouse were randomly divided into normal saline （NS） group, CnoA group, YIO1 low, middle, high dosage group （25, 50, 100 mg·kg^-1） and bifendate group （LB,150 mg·kg^- 1 ）. All groups, except for the NS group, were given CnoA aqueous solution （20 mg· kg^-1） via tail vein injection 1 hour after drug administration at d5 and d7, and the mouse were banned for eating but drinking at the last poisoning. 8 hours later, the eyeballs were promptly taken for blood samples, amt the livers were taken for determination of the levels of ALT, AST , liver oxidant-antioxidant, MDA, NO, SOD,GSH, and for the AI,T, AST and the contenls histopathology examination. of MDA and NO in the liver Results： Compares with the normal group, the activity of were raised significantly amt the liver and spleen index obviously elevated （P 〈0.01 ） , while the content of SOD and GSH in the liver and the thymus index was decreased obviously（P 〈 0.01 ）. Different doses of Y101 attenuated these changes in rats with immune hepatic injury in a dose-dependent manner. Give Y101 after treatment, medium and high dose group of liver histopathological changes were significantly lighter than moclel group. Conclusion：Y101 has protecting effect on immune hepatic injury induced by CnoA in mice, and mechanism is probably related to anti-oxidation.

关 键 词：苯丙氨酸二肽类化合物 Y101 刀豆蛋白A 保肝作用 

分 类 号：R975[医药卫生—药品]