Nrf2基因敲除对莪术神经发育毒性的影响研究  

Effect of Nrf2 Knock-out on Developmental Neurotoxicity Induced by Exposure of Mice to Ezhu(Rhizoma Curcumae)

作　　者：于春磊[1] 李成冲[1] 刘吉成[1] 董妙先[1] 牛英才[1] YU Chunlei;LI Chengchong;LIU Jicheng;DONG Miaoxian;NIU Yingcai(Institute of Medicine,Qiqihar Medical College,Qiqihar 161042,Heilongjiang,China)

机构地区：[1]齐齐哈尔医学院医药科学研究所,黑龙江齐齐哈尔161006

出　　处：《中华中医药学刊》2020年第8期110-113,共4页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金(81673686)。

摘　　要：目的观察莪术对正常和血瘀证孕小鼠子代的神经发育毒性是否具有选择性及可能的生物学机制。方法采用冰水浸入法制备寒凝血瘀证小鼠模型。C57BL/6野生小鼠和Nrf2基因敲除(Nrf2-KO)小鼠分为对照组和莪术暴露组,孕小鼠从妊娠第5~18天灌胃给予莪术水煎液。检测子代小鼠负趋地性达标日龄,分光光度法检测子代小鼠脑组织LPO含量和SOD活性,实时定量PCR检测子代小鼠脑组织SOD1和HO-1 mRNA表达,蛋白质印迹法检测子代小鼠脑组织HO-1蛋白表达。结果与正常对照组比较,正常小鼠灌胃莪术(10.0 g/kg)导致子代负趋地性达标日龄显著延长和脑组织LPO显著增加(均P<0.05),而血瘀证小鼠无显著差异(均P>0.05)。与正常对照组比较,血瘀证组小鼠HO-1表达,SOD活性和HO-1 mRNA表达显著增加(均P<0.05)。Nrf2基因敲除增加了血瘀证孕鼠子代断崖回避的达标日龄和脑组织氧化应激。结论莪术对正常小鼠子代的毒性效较血瘀证小鼠子代明显,Nrf2分子参与莪术神经发育毒性的有故无殒现象。Objective The aim of this study was to investigate whether there was selectivity on developmental neurotoxicity between normal and blood-stasis pregnant mice orally administered with Ezhu(Rhizoma Curcumae)and the underlying possible biologic mechanisms.Methods Cold coagulation and blood stasis mice model was induced by being immersed in ice water.C57 BL/6 mice and Nrf2 knock-out(KO)mice were randomized into control group and Ezhu(Rhizoma Curcumae)exposure groups.The pregnant mice were administered with Ezhu(Rhizoma Curcumae)during pregnant day 5 to day 18.The neurodevelopment reflex was examined by the positive occurring time of avoidance precipice reflex tests.Measurement of LPO content and SOD activity in brain of the offspring mice were performed by Colorimetric Assays.The expressions of SOD1 and HO-1 mRNA in brain of the offspring mice were examined by Real-Time RT-PCR,and HO-1 protein expression was examined by Western blotting.Results Compared with the normal control group,C57 BL/6 mice treated with Ezhu(Rhizoma Curcumae)(10.0 g/kg)extended the positive occurring time of negative geotaxis reflex of mice offsprings and increased LPO content in brain.We could not find out any significant change of blood-stasis pregnant mice offsprings.Compared with the normal control group,SOD activity and expressions of HO-1 mRNA and protein were up-regulated significantly in brain of the offsprings of blood-stasis pregnant mice.Nrf2 knock-out extended the positive occurring time of negative geotaxis reflex of offsprings of blood-stasis pregnant mice.Conclusions Developmental neurotoxicity induced by Ezhu(Rhizoma Curcumae)in the blood-stasis pregnant mice was weaker than that of the normal pregnant mice.Nrf2 activation is involved in"affecting the disease without injuring the body"phenomenon of Ezhu(Rhizoma Curcumae).

关 键 词：莪术 有故无殒 血瘀证 Nrf2敲除小鼠 

分 类 号：R285.1[医药卫生—中药学]