| 段 鹏,郭秦乐,刘 利,李晓青,白立曦,许 静.dl-3-正丁基苯酞对脑损伤大鼠的神经保护作用的实验研究[J].现代生物医学进展英文版,2020,(11):2024-2031. |
| dl-3-正丁基苯酞对脑损伤大鼠的神经保护作用的实验研究 |
| Neuroprotective Effect of dl-3-n-butylphthalide (NBP) on Rats with Brain Injury |
| Received:February 23, 2020 Revised:March 18, 2020 |
| DOI：10.13241/j.cnki.pmb.2020.11.005 |
| 中文关键词: dl-3-正丁基苯酞 创伤性颅脑外伤 抗氧化 神经元凋亡 脑水肿 |
| 英文关键词: dl-3-n-butylphthalide Traumatic craniocerebral trauma Antioxidant Neuronal apoptosis Cerebral edema |
| 基金项目:陕西省自然科学基础研究计划项目（2018JM7021）；西安交通大学第一附属医院基金自由探索项目（2019ZYTS-10） |
| Author Name | Affiliation | E-mail | | DUAN Peng | Department of Emergency, The First affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China | PiXumei@163.com | | GUO Qin-yue | Department of Critical Care Medicine, The First affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China | | | LIU Li | Department of Emergency, The First affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China | | | LI Xiao-qing | Department of Emergency, The First affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China | | | BAI Li-xi | Department of Emergency, The First affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China | | | XU Jing | Department of Emergency, The First affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China | |
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| 中文摘要: |
| 摘要 目的：研究dl-3-正丁基苯酞（NBP）对脑损伤大鼠的神经保护作用。方法：将100只7周龄清洁级雄性Sprague-Dawley（SD）大鼠随机分成5组，分别为假手术组、模型组、NBP低、中和高剂量组，每组20只。使用控制性皮层撞击损伤建立中型大鼠颅脑损伤模型。将NBP溶解在大豆油中，NBP低、中和高剂量组分别按照每天20、40和80 mg/kg的剂量灌胃，假手术组和模型组灌胃等体积的大豆油，共给药2周。采用改良神经功能缺损评分（mNSS）对大鼠的神经系统状况进行评价。检测各组大鼠治疗后的脑组织含水量以及脑组织中丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）水平。TUNEL方法鉴定细胞的凋亡。通过RT-PCR、Western blot或免疫组化检测脑组织中Nrf2、NQO-1、HO-1、ApoJ、MMP9、AQP4、Caspase-3和AKT的表达。结果：NBP治疗2周后，NBP低、中和高剂量组大鼠的mNSS评分和神经元凋亡率以剂量依赖性方式显著降低（P<0.05）。与模型组比较，NBP低、中和高剂量组大鼠的脑含水量均显著降低（P<0.05）。与模型组比较，NBP低、中和高剂量组大鼠的MDA显著降低，而SOD和GSH-Px显著升高（P<0.05）。与模型组比较，NBP低、中和高剂量组大鼠的细胞核Nrf2显著升高，而细胞质Nrf2显著降低（P<0.05）。与模型组比较，NBP低、中和高剂量组大鼠的NQO-1和HO-1蛋白表达水平显著升高（P<0.05）。与模型组比较，NBP低、中和高剂量组大鼠的AQP4、MMP-9、ApoJ和Caspase-3的mRNA和蛋白表达水平均显著降低，而AKT显著升高（P<0.05）。结论：NBP对创伤性颅脑外伤大鼠具有一定的神经保护作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the neuroprotective effect and mechanism of dl-3-n-butylphthalide (NBP) on rats with brain injury. Methods: A total of 100 7-week-old male Sprague-Dawley (SD) rats were randomly divided into 5 groups: sham group, model group, NBP low, medium and high dose groups, 20 in each group. A model of craniocerebral injury in rats was established using controlled cortical impact injury. NBP was dissolved in soybean oil. The low, medium and high dose groups of NBP were orally administered at a dose of 20, 40, and 80 mg / kg for 2 weeks, respectively. The sham group and the model group were orally administered with an equal volume of soybean oil. The modified neurological deficit score (mNSS) was used to evaluate the neurological status of rats. The brain tissue water content and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the brain tissues of each group were detected after treatment. TUNEL method was used to identify cell apoptosis. The expressions of Nrf2, NQO-1, HO-1, ApoJ, MMP9, AQP4, Caspase-3 and AKT in brain tissue were detected by RT-PCR, Western blot or Immunohistochemistry. Results: After 2 weeks of NBP treatment, the mNSS score and neuron apoptosis rate in the NBP treatment group were significantly reduced in a dose-dependent manner(P<0.05). Compared with the model group, the brain water content in the NBP treatment group was significantly reduced (P<0.05). Compared with the model group, MDA in the NBP treatment group was significantly reduced, while SOD and GSH-Px were significantly increased(P<0.05). Compared with the model group, the nuclear Nrf2 in the NBP treatment group was significantly increased, while the cytoplasmic Nrf2 was significantly decreased (P<0.05). Compared with the model group, the expression levels of NQO-1 and HO-1 proteins in the NBP treatment group were significantly increased(P<0.05). Compared with the model group, the mRNA and protein expression levels of AQP4, MMP-9, ApoJ, and Caspase-3 in the NBP low, medium, and high dose groups were significantly reduced, while AKT was significantly increased(P<0.05). Conclusion: NBP has a certain neuroprotective effect on rats with traumatic brain injury. |
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