| 卜 一,张 硕,钱旭东,王红梅,杨康梅,窦志杰.基于PI3K/AKT/mTOR信号通路探讨半枝莲总黄酮对脑缺血再灌注损伤大鼠神经功能和氧化应激损伤的影响[J].,2022,(18):3440-3446 |
| 基于PI3K/AKT/mTOR信号通路探讨半枝莲总黄酮对脑缺血再灌注损伤大鼠神经功能和氧化应激损伤的影响 |
| Investigate the Effects of Total Flavonoids from Scutellaria Barbata on Neurological Function and Oxidative Stress Injury in Rats with Cerebral Ischemia-Reperfusion Injury Based on PI3K/AKT/mTOR Signaling Pathway |
| 投稿时间：2022-03-24 修订日期：2022-04-21 |
| DOI：10.13241/j.cnki.pmb.2022.18.007 |
| 中文关键词: PI3K/Akt/mTOR信号通路 半枝莲总黄酮 脑缺血再灌注损伤 神经功能 氧化应激 |
| 英文关键词: PI3K/Akt/mTOR signaling pathway Total flavonoids from Scutellaria barbata Cerebral ischemia-reperfusion injury Neurological function Oxidative stress |
| 基金项目:承德市科学技术研究与发展计划项目（201904A100）；河北省自然科学基金项目（H2019406165） |
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| 中文摘要: |
| 摘要 目的：基于磷脂酰肌醇3激酶（PI3K）/丝氨酸苏氨酸蛋白激酶（Akt）/哺乳动物的雷帕霉素（mTOR）信号通路探究半枝莲总黄酮对脑缺血再灌注损伤（CIRI）大鼠神经功能和氧化应激损伤的影响。方法：选取70只SPF级雄性SD大鼠，采用线栓法制备大脑中动脉闭塞（MCAO）模型，将造模成功的60只大鼠随机分为模型组、半枝莲总黄酮低剂量组（半枝莲L组）、半枝莲总黄酮中剂量组（半枝莲M组）、半枝莲总黄酮高剂量组（半枝莲H组）、control组、LY294002组，每组10只，剩余10只大鼠作为sham组。半枝莲L、M、H组分别给予半枝莲总黄酮0.1、0.2、0.4 g/kg溶于2 mL生理盐水灌胃，control组给予尼莫地平0.3 g/kg溶于2 mL生理盐水灌胃，LY294002组给予半枝莲总黄酮0.4 g/kg溶于2 mL生理盐水灌胃，同时侧脑室注射PI3K抑制剂LY294002 20 μmol/L，模型组和sham组给予等量的生理盐水灌胃。分别比较各组大鼠神经功能评分、脑组织积水量、脑梗死体积、脑组织病理学变化、脑组织氧化应激水平、脑组织中p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白表达。结果：各组大鼠神经功能评分、脑组织含水量、脑梗死体积、丙二醛（MDA）水平比较，模型组明显高于sham组，半枝莲L、M、H组、control组均低于模型组，且半枝莲H组优于半枝莲L、M组，但LY294002组高于半枝莲H组（P<0.05）；各组大鼠超氧化物岐化酶（SOD）水平和p-PI3K/PI3K、p-Akt/Akt、p-mTOR/mTOR蛋白表达比较，模型组明显低于sham组，半枝莲L、M、H组、control组均高于模型组，且半枝莲H组优于半枝莲L、M组，但LY294002组低于半枝莲H组（P<0.05）。结论：半枝莲总黄酮可能通过激活PI3K/Akt/mTOR信号通路发挥对CIRI大鼠神经功能和氧化应激损伤的改善作用，且高剂量半枝莲总黄酮的改善作用最显著。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effects of total flavonoids from Scutellaria barbata on neurological function and oxidative stress injury in rats with cerebral ischemia-reperfusion injury (CIRI) rats based on phosphatidylinositol 3 kinase (PI3K)/serine threonine protein kinase (Akt)/mammalian rapamycin (mTOR) signaling pathway. Methods: 70 SPF grade male SD rats were selected to establish the middle cerebral artery occlusion (MCAO) model by suture method, 60 rats with successful modeling were randomly divided into model group, low-dose total flavonoids from Scutellaria barbata group (Scutellaria barbata L group), medium-dose total flavonoids from Scutellaria barbata group (Scutellaria barbata M group), high-dose total flavonoids from Scutellaria barbata group (Scutellaria barbata H group), control group and LY294002 group, with 10 rats in each group, the remaining 10 rats served as sham group. The Scutellaria barbata L, M, H groups were given total flavonoids from Scutellaria barbata 0.1, 0.2 and 0.4 g/kg dissolved in 2 mL normal saline by gavage, respectively, while control group was given nimodipine 0.3 g/kg dissolved in 2 mL normal saline by gavage. LY294002 group was given 0.4 g/kg total flavonoids from Scutellaria barbata dissolved in 2 mL normal saline by gavage, while PI3K inhibitor LY294002 20 μmol/L was injected into the lateral ventricle. Model group and sham group were given the same amount of normal saline by gavage. Neurological function score, brain tissue water volume, cerebral infarction volume, brain tissuehistopathological changes, brain tissue oxidative stress level, brain tissue p-PI3K/PI3K, P-Akt /Akt, p-MTOR /mTOR protein expression of rats in each group were compared. Results: Compared with the neurological function score, brain tissue water content, cerebral infarction volume and malondialdehyde (MDA) level of rats in each group, the model group were significantly higher than those in sham group, and Scutellaria barbata L, M, H and control groups were lower than those in model group, and Scutellaria barbata H group was better than Scutellaria barbata L, M group, but LY294002 group was higher than Scutellaria barbata H group(P<0.05). Compared with the level of superoxide dismutase(SOD) and p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR protein expression of rats in each group, the model group was significantly lower than the sham group, and the Scutellaria barbata L, M, H and control groups were all higher than the model group, and Scutellaria barbata H group was better than Scutellaria barbata L, M group, but LY294002 group was lower than the Scutellaria barbata H group (P<0.05). Conclusion: The total flavonoids from Scutellaria barbata may improve neural function and oxidative stress injury in CIRI rats by activating PI3K/Akt/mTOR signaling pathway, and the improvement effect of high dose total flavonoids from Scutellaria barbata is the most significant. |
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