| 王静怡,高娟娟,王彤歌.丁基苯酞调控沉默信息调节因子 1/核因子相关因子 2通路抑制缺血性脑卒中大鼠氧化应激损伤的实验研究[J].安徽医药,2021,25(2):233-237. |
| 丁基苯酞调控沉默信息调节因子 1/核因子相关因子 2通路抑制缺血性脑卒中大鼠氧化应激损伤的实验研究 |
| Inhibitory effect of butylphthalide on oxidative stress injury in ischemic stroke rats by regulating SIRT1/Nrf2 pathway |
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| DOI：10.3969/j.issn.1009-6469.2021.02.005. |
| 中文关键词: 卒中 脑梗死 丁基苯酞 氧化应激 机制 |
| 英文关键词: Stroke Brain Infarction Butylphthalide Oxidative stress Mechanism |
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| 中文摘要: |
| 目的观察丁基苯酞对缺血性脑卒中大鼠氧化应激的影响，并探讨其对沉默信息调节因子 1(SIRT1)/核因子相关因子 2(Nrf2)通路的调控机制。方法 2018年 3月至 2019年 3月， 50只成年雄性 SD大鼠采用随机数字表法分为假手术组、模型组和低、中、高剂量组 5组，每组 10只。建模且低、中、高剂量组分别腹腔注射 40、80、160 mg/kg丁基苯酞，余均腹腔注射等量生理盐水。 Zea Longa评分标准评价神经功能缺损；苏木素 -伊红(HE)染色观察各组脑组织病理学变化；化学比色法检测各组脑皮质组织丙二醛( MDA)、超氧化物歧化酶( SOD)、谷胱甘肽过氧化物酶( GSH-PX)的活性；实时聚合酶链反应( qRT-PCR)检测脑皮质组织 SIRT1、Nrf2 mRNA表达；蛋白质印迹法(Western Blot)检测脑皮质组织 SIRT1、Nrf2蛋白表达。结果给药后假手术组神经功能缺损评分无明显变化( P > 0.05)模型组评分给药后明显高于给药前［( 3.12±0.30)分比( 2.67±0.23)分， P<0.05］给药前后低［( 2.69±0.25)分比( 1.96±0.23)分］、，中［( 2.67±0.22)分比( 1.20±0.17)分］、高［(2.65±0.24)分比( 0.85±0.22)分］剂量组评，分均下降(P < 0.05)，且呈剂量依赖性；假手术组脑皮质组织基本无病理改变，余 4组均呈病理变化，低、中、高剂量组均较模型组病理变化有所改善，且呈剂量依赖性；模型组 MDA、SOD、GSH-PX的活性均明显异常(P < 0.05)，且低、中、高剂量组均较模型组的活性明显改善(P < 0.05)，效果呈剂量依赖性；模型组 SIRT1、Nrf2 mRNA及蛋白表达均下降(P < 0.05)，低、中、高剂量组较模型组 mRNA及蛋白表达均升高(P < 0.05)，且呈剂量依赖性。结论对缺血性脑卒中大鼠给予丁基苯酞可减轻神经功能缺损和脑组织病理改变，控制脑皮质氧化应激反应，推测可能是通过调控 SIRT1/Nrf2通路，上调 SIRT1、Nrf2 mRNA及蛋白表达实现的。 |
| 英文摘要: |
| Objective To observe the effect of butylphthalide on oxidative stress in rats with ischemic stroke and to explore its regulation mechanism on silence Information Regulator 1 (SIRT1)/Nuclear Factor Related Factor 2 (Nrf2) pathway.Methods Fifty adult maleSDratswererandomlydividedint of ivegroupsfrom March 2018toMarch2019.Thelow,middleandhighdosegroupsweregivenintraperitoneal injection of 40, 80 and 160 mg/kg respectively, and the rest were given intraperitoneal injection of normal saline. Zea Longa score wasused to evaluate neurological impairment.Hematoxylin-eosin (HE) staining was used to observe the pathological changes of brain tissue ineachgroup.Theactivities of malondialdehyde (MDA),superoxidedismutase (SOD)andglutathioneperoxidase (GSH-PX)incerebralcortex were detected by chemical colorimetry.Real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of SIRT1 andNrf2 in cerebral cortex. The SIRT1 and Nrf2 protein expressions in cerebral cortex by Western Blot were detected.Results There was no significant change in neurological deficit score in the sham-operated group after administration(P > 0.05), and the score in the model group was significantly higher than that before administration[(3.12±0.30) vs. (2.67±0.23),P < 0.05].The low[(2.69±0.25)vs.(1.96±0.23)],middle [(2.67±0.22)vs(1.20±0.17)]and highdosegroups[(2.65±0.24)vs.(0.85±0.22)]weresignificantlyimproved(P < 0.05),anditwasdose-dependent.There were no pathological changes in cerebral cortex in sham-operated group,and pathological changes were found in the remaining four groups.The three-dose group was better than the model group and showed a dose-dependent manner.The activities of MDA, SOD and GSH-PX in the model group were significantly abnormal (P < 0.05),and the three dose groups were significantly improved compared with the model group(P < 0.05),the effect was dose-dependent.The expression of SIRT1 and Nrf2 in the model group decreased (P < 0.05), and the expression of SIRT1 and Nrf2 in the three dose groups was higher than that in the model group (P < 0.05), and it was dose-dependent.Conclusion Butylphthalide can alleviate neurological impairment and pathological changes of brain tissue and control oxidativestress in cerebral cortex in rats with ischemic stroke, presumably by up-regulating the expression of SIRT1 and Nrf2 by regulating SIRT1/Nrf2 pathway. |
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