人参皂苷RH2对MCAO大鼠血管新生的调节  

Effects of ginsenoside RH2 on neovascularization of rats with middle cerebral artery occlusion

作　　者：谢靖[1] 梁华峰[1] 祁鸣[1] 高惠春 郑玺 XIE Jing;LIANG Huafeng;QI Ming;GAO Huichun;ZHENG Xi(Department of Neurology, First Affiliated Hospital, Medical College of Shihezi University, Shihezi 832008 , China;Department of Neurology, Fukang People’s Hospital, Fukang 831500 , China;Department of Neurology, No. 474 Hospital of PLA, Urumchi 830000 , China)

机构地区：[1]石河子大学医学院第一附属医院神经科,新疆石河子832008 [2]新疆阜康市人民医院神经科,新疆阜康831500 [3]解放军第四七四医院神经科,新疆乌鲁木齐830000

出　　处：《中国病理生理杂志》2018年第1期112-117,共6页Chinese Journal of Pathophysiology

摘　　要：目的:探讨人参皂苷RH2(ginsenoside RH2,GS-RH2)对大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型大鼠血管新生的调节作用及潜在的作用机制。方法:取健康雄性SPF级大鼠随机分为假手术组、模型组(MCAO组)和实验组(GS-RH2组),每组18只。各组经相应处理后,观察并分析动物的一般生存状况及神经功能评分;并在干预的第1、3和7天测定微血管密度(microvessel density,MVD)、脑组织中丙二醛(malondialdehyde,MDA)的含量及超氧化物歧化酶(superoxide dismutase,SOD)和谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)的活性;同时采用Western blot检测脑组织中Kelch样环氧氯丙烷相关蛋白1(Kelch-like ECH-associated protein 1,Keap1)、核因子E2相关因子2(nuclear factor E2-related factor 2,Nrf2)及血红素加氧酶1(heme oxygenase-1,HO-1)的蛋白表达水平。结果:与假手术组相比,模型组大鼠出现明显的神经行为障碍,脑梗死体积显著增加,且神经功能评分显著升高(P<0.05);与模型组相比,干预7 d之后,GS-RH2组动物神经行为症状得到明显改善,脑梗死体积显著减小,神经功能评分显著降低(P<0.05)。微血管密度分析显示,随动物生存时间的延长,实验组大鼠MVD值呈升高的趋势,而模型组大鼠MVD值则呈下降趋势,且在第7天时,实验组MVD值显著高于模型组(P<0.05)。与假手术组相比,各时间点模型组MDA的含量均升高,SOD和GSH-Px的活性均降低;与模型组相比,干预7 d之后,GS-RH2组MDA的含量降低,SOD和GSH-Px的活性升高(P<0.05)。Western blot结果显示,与模型组相比,干预7 d之后,实验组Nrf2及HO-1蛋白表达显著增加,Keap1蛋白表达显著减少。结论:人参皂苷RH2可促进MCAO大鼠血管新生,其作用机制可能与激活Keap1/Nrf2信号通路、提高抗氧化酶的活性从而抑制氧化应激反应有关。AIM:To investigate the effects of ginsenoside RH2(GS-RH2)on neovascularization of rats with middle cerebral artery occlusion(MCAO)and its potential mechanisms.METHODS:SPF Sprague-Dawley rats were randomly divided into sham operation(sham)group,MCAO model(MCAO)group and GS-RH2group,with18rats in each group.After surgery,the general condition and neurological function score of the rats were assessed.At the1st day,3rd day and7th day after intervention,the microvessel density(MVD),the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were examined.The protein expression of kelch-like ECH-associated protein1(Keap1),nuclear factor E2-related factor2(Nrf2)and heme oxygenase-1(HO-1)was determined by Western blot.RESULTS:Compared with sham group,the rats in MCAO group showed significant neurobehavioral obstacles and ischemic brain infarction with higher neurological function score,while treatment with GS-RH2significantly improved behavioral impairment and reduced the infarction volume with lower neurological function score.The MVD score in GS-RH2group was increased as the animal survival time prolonged,while the MVD score in MCAO group was decreased.After intervention for7d,the MVD score in GS-RH2group was significantly higher than that in MCAO group(P<0.05).Compared with sham group,the content of MDA was increased and the activities of SOD and GSH-Px were decreased in MCAO group at each time point.After intervention for7d,the MDA content was decreased and the SOD and GSH-Px activities were increased in GS-RH2group compared with MCAO group.After intervention for7d,the protein expression of Nrf2and HO-1was increased,while the protein expression of Keap1was decreased in GS-RH2group compared with MCAO group(P<0.05).CONCLUSION:Ginsenoside RH2promotes neovascularization of MCAO model rats.The mechanism may be related to the activation of Keap1/Nrf2signaling pathway,promotion of the antioxidant enzyme activity and inhibition of oxidative stress.

关 键 词：人参皂苷RH2 大脑中动脉闭塞 氧化应激 血管新生 Keap1/Nrf2信号通路 

分 类 号：R743.3[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]