白藜芦醇苷对脑梗死大鼠中Shh和Nrf2信号通路的调节及机制研究  

Regulation and mechanism of polydatin on Shh and Nrf2 signaling pathways in focal cerebral ischemia in rats

作　　者：季辉[1] 刘莹[1] 王力娜[1] 孙倩[1] 崔丽丽[1] 张祥建[1] 刘晓霞[1] Ji Hui;LiuYing;Wang Lina;Sun Qian;Cui Lili;Zhang Xiangjian;Liu Xiaoxia(Department of Neurology,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院神经内科,石家庄050000

出　　处：《脑与神经疾病杂志》2021年第9期533-538,共6页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金会项目(81401098);河北省卫健委青年科技课题(20180325)。

摘　　要：目的观察大脑皮质Shh信号通路的转录因子Gli1、Ptch1与SOD1的动态表达,并探讨白藜芦醇苷脑保护作用及其对Gli1、Ptch1、Nrf2及SOD1的调节作用。方法采用线栓法建立大鼠永久性大脑中动脉闭塞模型。实验(一):SD大鼠随机分为7组:正常对照组以及建立局灶性缺血模型成功后3 h、6h、12 h、24 h、48 h、72 h共7个观察组,采用免疫组织化学方法、Western blot及RT-PCR观察缺血周围区Gli1,Ptch1和SOD1表达的变化。实验(二):SD大鼠随机分为4组:假手术组、溶剂对照组、和给药组(白藜芦醇苷25mg,50mg·kg^(-1))。术后24h和72 h分别采用免疫组织化学方法、Western blot及RT-PCR观察缺血周围区Gli1,Ptch1,Nrf2和SOD1表达的变化。结果免疫组织化学、Western blot及RT-PCR显示脑缺血6 h后Glil、Ptch1以及SOD1的表达开始升高,并于24 h达高峰,72 h后开始降低。白藜芦醇苷50mg·kg^(-1)能改善大鼠缺血后神经功能评分、减少梗死体积,显著升高缺血后Gli1、Ptch1、Nrf2和SOD1表达量的升高。结论大剂量白藜芦醇苷对局灶性脑缺血具有神经保护的作用。其保护作用可能与上调Gli1、Ptch1、Nrf2及SOD1的表达有关。Objective To observe the dynamic expression of transcription factors Glil,Ptch1 and SOD1 in Shh signaling pathway in cerebral cortex,and to study the protective effect of polydatin and the regulatory effect of Glil Ptch1,Nrf2 and SOD1 in focal cerebral ischemia in rats.Method The permanent model of middle cerebral artery occlusion(MCAO)in rats was established by suture plug method.Experiment 1:SD rats were randomly divided into 7 groups:normal control group,and groups at 3 h,6 h,12 h,24 h,48 h and 72 h after successful establishment of focal ischemia model.The expression of Glil,Ptch1 and SOD1 in the ischemic peripheral area was observed by immunohistochemical,Western blot and RT-PCR.Experiment 2:SD rats were randomly divided into 4 groups:sham operation group,vehicle group and treatment group(polydatin 25 mg,50 mg·kg^(-1)).The expressions of Gli1,Ptch1,Nrf2 and SOD1 in the ischemic peripheral area were observed by Western blot and RT-PCR 24 h and 72 h after surgery.Result Immunohistochemical,Western blot and RT-PCR showed that the expression of Glil,Ptch1 and SOD1 began to increase 6 h after cerebral ischemia,and reached the peak at 24 h.The reduction of polydatin(50 mg·kg^(-1))at 72 h after cerebral ischemia could improve the neurological function score and reduce the infarct volume,and significantly increased the expression of Gli1,Ptch1,Nrf2 and SOD1 after cerebral ischemia.Conclusion Polydatin(50 mg·kg^(-1))has neuroprotective effect on focal cerebral ischemia in rats.The protective effect may be related to the up-regulation of the expression of Glil,Ptch1,Nrf2 and SOD1.

关 键 词：白藜芦醇苷 脑梗死 GLI1 Ptch1 NRF2 

分 类 号：R743.34[医药卫生—神经病学与精神病学]