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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 |
| 作者： | 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 |
| 阅读数： | 260 次 |
| 本月下载数： | 8 次 |
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