【作者】 曾灵娜； 马致洁； 王伽伯； 李宝才； 李奇； 蒋冰倩； 吕旸； 赵艳玲； 张萍； 方芳； 肖小河；

【Author】 Ling-na Zeng 1,3,Zhi-jie Ma 1,4,Jia-bo Wang 1 ,Bao-cai Li 3,Qi Li 1,Bing-qian Jiang 1,Yang Lü 1,Yan-ling Zhao 1,Ping Zhang 1,Fang Fang 1,4 and Xiao-he Xiao 2 1 China Military Institute of Chinese Medicine,302 Military Hospital,Beijing,China 2 Integrative Medicine Center,302 Military Hospital,Beijing,China 3 Faculty of Life Science and Technology,Kunming University of Science and Technology,Kunming,China 4 College of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu,China

【机构】 解放军302医院全军中医药研究所； 昆明理工大学生命科学院； 成都中医药大学药学院； 解放军302医院中西医结合医学中心；

【摘要】 近年来,重金属铬污染引起的中毒事件如云南曲靖铬渣事件、毒胶囊事件等频发,严重影响公众健康。机体摄入过量铬会导致严重的肾毒性,而有关治疗药物的研究较少。本文报道了中药大黄对铬致肾衰竭大鼠模型的保护作用及可能的机制:通过平行对比大黄总提物(TR)、总蒽醌部位(TA)、总鞣质部位(TT)和其他部位(RC)对六价铬致肾衰的保护作用,首次发现TT可能是大黄治疗铬致肾毒性的主要物质基础,而TA反而会加重铬致肾损伤,RC作用不明显;根据六价铬致肾毒性产生的体内机制和TT的化学性质,针对性考察了TT的抗氧化和还原作用,证实TT具有较强的羟自由基(.OH)清除能力,并首次发现TT能在低浓度将高毒性的六价铬还原为低毒性的三价铬,可有效阻断铬离子在体内产生.OH的循环反应,并且TT在较高浓度时可将铬离子还原产物沉淀,有利于在胃肠道阻断铬的吸收。综合上述结果,本文首次提出了大黄总鞣质部位保护铬致肾毒性的多途径抗氧化机制,显示大黄鞣质作为铬毒性保护剂具有良好的开发前景,有待深入阐明其具体的活性物质结构。该研究也拓展了对植物鞣质药理活性的认识,为从植物中筛选高效的铬等重金属毒性保护剂提供了参考。更多还原

【Abstract】 Chromium nephrotoxicity,one of the major causes of heavy metal-induced public health problems,is thought to occur through the oxidant lesion mechanism.There is still a lack of specific remedies against chromium nephrotoxicity.We primarily screened Chinese herbal medicines with a potential protective effect against chromium nephrotoxicity,e.g.,rhubarb(Rheum palmatum L.).However,the active constituents in rhubarb and its mechanisms remain unclear.In this study,the total rhubarb extract(TR) was successively separated into three parts:total anthraquinone extract(TA),total tannin extract(TT) and remaining component extract(RC).The pharmacological effects of each extract on the potassium dichromate(K 2 Cr 2 O 7)-induced nephrotoxicity in rats were comparatively evaluated by biochemical tests and histopathological analyses.The results showed that the different parts of the constituents revealed diverse activities.Only the administration of TT protected the kidney function in rats with K 2 Cr 2 O 7-induced nephrotoxicity.In contrast,both TR and TA further aggravated the kidney injury in K 2 Cr 2 O 7-injured rats.RC showed no significant effects.An in vitro experiment demonstrated the significant activity of TT to scavenge hydroxyl radicals,which is considered to be the dominant lesion product generated by hexavalent chromium(Cr(VI)).TT also showed a reduced ability to transform toxic high valence chromium ions into non-toxic low valence ions at low concentrations of TT.It was able to further precipitate with chromium at high concentrations.These results suggested that rhubarb tannins protect rats against K 2 Cr 2 O 7-induced nephrotoxicity as a free radical scavenger,reductant,and metal precipitant.The multiple protective routes of this herbal medicine might make rhubarb a superior option for development into a promising natural remedy against chromium nephrotoxicity.更多还原