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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
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篇名: 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
TITLE: Study on Improvement Effects of Icariside Ⅱ on Neurological Function of Focal Cerebral Ischemia Model Rats by Regulating miR- 141-3p/Notch/Nrf2 Axis
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(20mg/kg)和ICSⅡ低、中、高剂量组(4、8、16mg/kg),每组20只。构建局灶性脑缺血大鼠模型24h后,分别灌胃生理盐水或相应药物,每天2次,连续给药3d。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Westernblotting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。
ABSTRACT: OBJECTIVE:To study the improvement effects of icariside Ⅱ(ICS Ⅱ)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 ICS Ⅱ low-dose,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 re levant 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 qRT-PCR ;the protein expression of Notch and Nrf 2 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 Nrf 2 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 Nrf 2 in cerebral tissue were significantly increased in ICS Ⅱgroups(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 significantly. CONCLUSIONS :ICS Ⅱ can promote the recovery of neurological function in focal cerebral ischemic model rats ,which may be related to down-regulation of miR-141-3p and activation of Notch/Nrf 2 axis.
期刊: 2020年第31卷第19期
编辑: 高琛,支应鹏
AUTHORS: GAO Chen,ZHI Yingpeng
关键字: 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
KEYWORDS: Icariside Ⅱ;miR-141-3p;Notch;Nuclear factor erythroid- 2-related factor 2;Focal cerebral ischemia model ;Rats
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