淫羊藿次苷Ⅱ调节miR-141-3p/Notch/Nrf2轴对局灶性脑缺血模型大鼠神经功能的改善作用研究  

Study on Improvement Effects of IcarisideⅡon Neurological Function of Focal Cerebral Ischemia Model Rats by Regulating miR-141-3p/Notch/Nrf2 Axis

作　　者：高琛[1] 支应鹏 GAO Chen;ZHI Yingpeng(Dept.of Encephalopathy,Jinan Hospital of TCM,Jinan 250012,China;Dept.of Hypertension,Jinan Hospital of TCM,Jinan 250012,China)

机构地区：[1]济南市中医医院脑病科,济南250012 [2]济南市中医医院高血压科,济南250012

出　　处：《中国药房》2020年第19期2386-2391,共6页China Pharmacy

基　　金：山东省中医药科技发展计划项目(No.2019-0555)。

摘　　要：目的:研究淫羊藿次苷Ⅱ(ICSⅡ)通过调节微核醣核酸-141-3p/Notch信号通路/核因子E2相关因子2(miR-141-3p/Notch/Nrf2)轴对局灶性脑缺血模型大鼠神经功能的改善作用。方法:将大鼠分为假手术组、模型组、尼莫地平组(20 mg/kg)和ICSⅡ低、中、高剂量组(4、8、16 mg/kg),每组20只。构建局灶性脑缺血大鼠模型24 h后,分别灌胃生理盐水或相应药物,每天2次,连续给药3 d。对各组大鼠神经功能缺损进行评分;采用2,3,5-三苯基氯化四氮唑(TTC)染色法测定大鼠脑梗死体积;测定大鼠脑组织含水量、血脑屏障通透性;采用苏木精-伊红(HE)染色法观察大鼠脑组织病理学变化;采用实时荧光定量PCR法测定大鼠脑组织中miR-141-3p表达水平;采用Western blotting法测定大鼠脑组织中Notch、Nrf2蛋白表达水平。结果:与假手术组比较,模型组大鼠神经功能缺损评分和脑组织中Notch-1、Nrf2蛋白表达水平显著降低(P<0.05),脑梗死体积、脑组织含水量、血脑屏障通透性、miR-141-3p表达水平显著升高(P<0.05);脑皮质细胞分布杂乱,可见大量神经细胞炎性浸润和坏死。与模型组比较,ICSⅡ各剂量组大鼠神经功能缺损评分和脑组织中Notch-1、Nrf2蛋白表达水平均显著升高(P<0.05),脑梗死体积、脑组织含水量、血脑屏障通透性、miR-141-3p表达水平显著降低(P<0.05);脑皮质细胞排列规则,神经细胞炎性浸润和坏死数明显减少。结论:ICSⅡ能促进局灶性脑缺血模型大鼠神经功能的恢复,这可能与下调miR-141-3p水平,从而激活Notch/Nrf2轴有关。OBJECTIVE:To study the improvement effects of icarisideⅡ(ICSⅡ)on neurological function of focal cerebral ischemia model rats by regulating miR-141-3p/Notch/nuclear factor erythroid-2-related factor 2(Nrf2)axis(miR-141-3p/Notch/Nrf2).METHODS:The rats were divided into sham operation group,model group,nimodipine group(20 mg/kg)and ICSⅡlowdose,medium-dose and high-dose groups(4,8,16 mg/kg),with 20 rats in each group.Twenty-four hours after establishing focal cerebral ischemia model,model rats were given relevant medicine or normal saline intragastrically,twice a day,for consecutive 3 d.The neurological deficit of rats in each group was scored;the volume of cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride(TTC)staining;water content of cerebral tissue and the permeability of blood-brain barrier were measured;HE staining was performed to observe the pathological change of cerebral tissue of rats;the expression of miR-141-3p in cerebral tissue of rats was measured by q RT-PCR;the protein expression of Notch and Nrf2 in cerebral tissue of rats were measured by Western blotting assay.RESULTS:Compared with sham operation group,the neurological deficit score,expression of Notch-1 and Nrf2 in model group were significantly lowered(P<0.05);infarction volume,brain water content,the permeability of blood-brain barrier and the expression of miR-141-3p in cerebral tissue were increased significantly(P<0.05);the distribution of cortical cells was disordered,and inflammatory infiltration and necrosis were observed in a large number of nerve cells.Compared with model group,the neurological deficit score,the protein expression of Notch-1 and Nrf2 in cerebral tissue were significantly increased in ICSⅡgroups(P<0.05);infarction volume,brain water content,the permeability of blood-brain barrier and the expression of miR-141-3p in cerebral tissue were decreased significantly(P<0.05);the arrangement of cortical cells was regular,and the inflammatory infiltration and necrosis of nerve cells were decreased sig

关 键 词：淫羊藿次苷Ⅱ 微核醣核酸-141-3p NOTCH信号通路 核因子E2相关因子2 局灶性脑缺血模型 大鼠 

分 类 号：R285.5[医药卫生—中药学]