绞股蓝皂苷对奥沙利铂所致大鼠神经毒性保护作用及机制研究  

Protective Effect of Gypenoside on Peripheral Nerve Toxicity Induced by Oxaliplatin in Rats and Its Mechanism

作　　者：余伟 赵博[2] 张秀 黄乔 左斌 吴杰[2] YU Wei;ZHAO Bo;ZHANG Xiu;HUANG Qiao;ZUO Bin;WU Jie(The First Cinical Medical School of China Three Gorges University&Hubei Yichang People’s Hospital,Hubei Yichang 443002,China;Medical College of China Three Gorges University,Hubei Yichang 443002,China)

机构地区：[1]三峡大学第一临床学院湖北省宜昌市中心人民医院,宜昌443002 [2]三峡大学医学院,宜昌443002

出　　处：《天然产物研究与开发》2018年第10期1782-1786,1673,共6页Natural Product Research and Development

基　　金：国家自然科学基金(81402958);湖北省教育厅科学技术研究计划优秀中青年人才项目(Q20141208);三峡大学科学基金(KJ2012B061)

摘　　要：本研究主要探讨绞股蓝皂苷(Gypenoside,GPS)对奥沙利铂所致大鼠周围神经毒性保护作用及其分子机制。将雄性SD大鼠随机分为正常对照组、模型对照组、GPS低、中、高剂量组。除正常对照组外,其他各组均腹腔注射奥沙利铂4 mg/kg,同时模型对照组灌胃给予溶媒5%葡萄糖,GPS低、中和高分别灌胃给予50、100和200 mg/kg GPS,定期检测温度和机械刺激下大鼠行为变化,给药40天后处死大鼠。ELISA检测血浆中NGF含量,Western blot检测L4-5背根神经节中Nrf2及其下游NQO-1和HO-1蛋白表达水平。结果,与正常对照组相比,模型对照组出现明显行为学改变、血浆NGF下降,Western blot检测发现Nrf2及其下游NQO-1和HO-1蛋白表达水平显著下降。而给予GPS后可显著改善大鼠行为学改变; GPS低中高剂量组可上调Nrf2及其下游NQO-1和HO-1水平。综上所述,GPS可改善奥沙利铂所致大鼠周围神经毒性温度和机械刺激下的行为学改变,其机制与上调NGF水平以及Nrf2信号通路有关。To explore the protective effects and its molecular mechanism of action of gypenoside(GPS)on the improvement of peripheral nerve toxicity induced by oxaliplatin in rats.Male SD rats were randomly divided into normal control group,model control group,the low-,medium-and high-dose of GPS groups.Except of the normal control group,peripheral nerve toxicity rat models were established by intraperitomeal injection with oxaliplatin(4 mg/kg),meanwhile,different doses of GPS were given by gavage,the behavior changes of rats under mechanical stimulation and temperature were observed at different point time.At the end of the experiment,rats were sacrificed,the levels of serum NGF were determined by ELISA,and the relative expression levels of Nrf2 and its downstream molecular NQO-1,HO-1 in L4-5 dorsal root ganglion were detected by Western blot.Results:When compared with the normal control group,the mechanical withdrawal threshold and the cold stimulus response threshold were significantly reduced in the model control group.In addition,the levels of serum NGF and the protein expression levels of Nrf2,NQO-1 and HO-1 in L4-5 dorsal root ganglion were significantly reduced.Conversely,GPS significantly elevated threshold of mechanical withdrawal and cold stimulus response,significantly increased the levels of NGF in serum and the relative expression levels of Nrf2,NQO-1 and HO-1 protein in L4-5 dorsal root ganglion.In conclusion,GPS improves oxaliplatin-induced peripheral nerve toxicity by increasing the levels of serum NGF and upregulating the Nrf2 signal.

关 键 词：奥沙利铂 绞股蓝皂苷 神经毒性 背根神经节 Nrf2信号 

分 类 号：R966[医药卫生—药理学]