[1]李 亮,蒋晓帆,李 侠,等.肉苁蓉苯乙醇苷调控GSK3β/Nrf2/ARE通路减轻脑中动脉梗死大鼠氧化应激损伤实验研究[J].陕西医学杂志,2023,52(6):660-665.[doi:DOI:10.3969/j.issn.1000-7377.2023.06.006]
　LI Liang,JIANG Xiaofan,LI Xia,et al.Cistanche deserticola phenylethanoside alleviates oxidative stress injury in rats with middle cerebral artery occlusion by regulating GSK3β/Nrf2/ARE signaling pathway[J].,2023,52(6):660-665.[doi:DOI:10.3969/j.issn.1000-7377.2023.06.006]
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肉苁蓉苯乙醇苷调控GSK3β/Nrf2/ARE通路减轻脑中动脉梗死大鼠氧化应激损伤实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年6期
页码:
660-665
栏目:
基础研究
出版日期:
2023-06-05

文章信息/Info

Title:
Cistanche deserticola phenylethanoside alleviates oxidative stress injury in rats with middle cerebral artery occlusion by regulating GSK3β/Nrf2/ARE signaling pathway
作者:
李 亮; 蒋晓帆; 李 侠; 张 婵; 余 良
(空军军医大学西京医院,陕西 西安 710032)
Author(s):
LI Liang; JIANG Xiaofan; LI Xia; ZHANG Chan; YU Liang
(Xijing Hospital,Air Force Medical University,Xi'an 710032,China)
关键词:
肉苁蓉苯乙醇苷;  脑中动脉梗死;  氧化应激;  糖原合成酶激酶3β;  核因子E2相关因子2;  抗氧化反应元件;  信号通路
Keywords:
Cistanche deserticola phenylethanoside;  Middle cerebral artery occlusion;  Oxidative stress;  Glycogen synthase kinase 3β;  Nuclear factor E2-related factor 2;  Antioxidant response element;  Signaling pathway
分类号:
R 285.5
DOI:
DOI:10.3969/j.issn.1000-7377.2023.06.006
文献标志码:
A
摘要:
目的:观察肉苁蓉苯乙醇苷减轻脑中动脉梗死(MCAO)大鼠氧化应激损伤的作用,并通过糖原合成酶激酶3β(GSK3β)/核因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)信号通路探讨其发挥作用的机制。方法:将100只SD大鼠随机分为假手术组、模型组、阳性对照组以及肉苁蓉苯乙醇苷低、高剂量组,各20只。除假手术组外,其余组采用大脑中动脉线栓法制备MCAO模型,再灌注2 h后阳性对照组给予尼莫地平(12 mg/kg),肉苁蓉苯乙醇苷低、高剂量组分别给予肉苁蓉苯乙醇苷150、300 mg/kg灌胃,每日1次,连续14 d。对各组大鼠进行神经功能评分和脑组织含水量检测。采用2,3,5-氯化三苯基四氮唑(TTC)和尼氏(Nissl)染色法观察大鼠脑梗死及海马组织损伤情况。采用酶联免疫吸附法(ELISA)检测大鼠血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和丙二醛(MDA)活性。采用Western blot及反转录聚合酶链式反应(RT-PCR)检测海马组织GSK3β、Nrf2、血红素氧化酶-1(HO-1)蛋白和mRNA表达。结果:与假手术组比较,模型组神经功能评分、脑组织含水量和脑梗死占比明显增高(均P<0.05); 海马组织神经元受损; 血清SOD、GSH-Px水平降低,MDA含量增加(均P<0.05); 海马组织GSK3β蛋白和mRNA表达升高,Nrf2、HO-1蛋白和mRNA表达降低(均P<0.05)。与模型组比较,肉苁蓉苯乙醇苷低、高剂量组神经功能评分降低,脑含水量和脑梗死占比减小(均P<0.05); 海马组织损伤程度得到有效减轻; 血清SOD和GSH-Px水平升高,MDA含量降低(均P<0.05); 海马组织中GSK3β蛋白和mRNA表达下调,Nrf2、HO-1蛋白和mRNA表达上调(均P<0.05)。结论:肉苁蓉苯乙醇苷可有效保护MCAO大鼠脑组织损伤,提高神经功能,改善抗氧化能力,其机制可能与活化GSK3β/Nrf2/ARE信号通路从而激活抗氧化系统相关。
Abstract:
Objective:To observe the effect of Cistanche deserticola phenylethanolide on oxidative stress injury in rats with middle cerebral artery occlusion(MCAO),and to explore the possible mechanism of its action through glycogen synthase kinase 3β(GSK3β)/nuclear factor E2-related factor 2(Nrf2)/antioxidant response element(ARE)signaling pathway.Methods:A total of 100 SD rats were randomly divided into sham operation group,model group,positive control group,Cistanche deserticola phenylethanolide low-dose group and Cistanche deserticola phenylethanolide high-dose group,with 20 rats in each group.Except for the sham operation group,the MCAO model was prepared by middle cerebral artery wire bolus method in the other groups.After 2 hours of perfusion,the positive control group was given nimodipine(12 mg/kg),and the Cistanche deserticola phenylethanolide low- and high-dose groups were given Cistanche deserticola phenylethanolide 150,300 mg/kg by gavage respectively,once a day for 14 consecutive days.The neurological function score and brain water content were detected in each group.TTC and Nissl staining were used to observe cerebral infarction and hippocampal tissue damage in rats.The activities of SOD,GSH-Px and MDA in serum were detected by ELISA.The protein and mRNA expressions of GSK3β,Nrf2 and heme oxygenase-1(HO-1)in hippocampus were detected by Western blot and RT-PCR.Results:Compared with the sham operation group,the neurological function score,brain water content and the proportion of cerebral infarction were significantly increased in the model group(all P<0.05); the hippocampal neurons were severely damaged; the levels of SOD and GSH-Px in serum were significantly decreased,and the content of MDA was significantly increased(all P<0.05); the protein and mRNA expressions of GSK3β in hippocampus were significantly increased,while the protein and mRNA expressions of Nrf2 and HO-1 were significantly decreased(all P<0.05).Compared with the model group,the neurological function scores,brain water content and the proportion of cerebral infarction were significantly reduced in the Cistanche deserticola phenylethanolide low- and high-dose groups(all P<0.05); the degree of hippocampal injury was effectively reduced; the serum SOD and GSH-Px levels were significantly increased,and the MDA content was decreased(all P<0.05); the protein and mRNA expression levels of GSK3β were down-regulated,and the protein and mRNA expression levels of Nrf2 and HO-1 were up-regulated in hippocampus(all P<0.05).Conclusion:Cistanche deserticola phenylethanolide can effectively protect the brain tissue damage of MCAO rats,improve neurological function antioxidant capacity,and its mechanism may be related to the activation of GSK3β/Nrf2/ARE signaling pathway to activate the antioxidant system.

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备注/Memo

备注/Memo:
基金项目:陕西省重点研发计划项目(2022SF-205)
更新日期/Last Update: 2023-06-05