文章摘要
李思雨,江伟,肖农.适宜浓度视黄酸对缺氧缺血性脑损伤后神经修复及PI3K/Akt信号通路的影响[J].中华物理医学与康复杂志,2024,46(12):1079-1084
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适宜浓度视黄酸对缺氧缺血性脑损伤后神经修复及PI3K/Akt信号通路的影响
  
DOI:10.3760/cma.j.cn421666-20240418-00280
中文关键词: 视黄酸  缺氧缺血性脑损伤  PI3K/Akt信号通路
英文关键词: Retinoic acid  Hypoxia  Ischemia  Brain damage  PI3K/Akt pathway
基金项目:国家自然科学基金面上项目(81571091)
作者单位
李思雨 重庆医科大学附属儿童医院康复科国家儿童健康与疾病临床医学研究中心儿童发育疾病研究教育部重点实验室儿童发育重大疾病国家国际科技合作基地儿童神经发育与认知障碍重庆市重点实验室重庆 400010 
江伟 重庆医科大学附属儿童医院康复科国家儿童健康与疾病临床医学研究中心儿童发育疾病研究教育部重点实验室儿童发育重大疾病国家国际科技合作基地儿童神经发育与认知障碍重庆市重点实验室重庆 400010 
肖农 重庆医科大学附属儿童医院康复科国家儿童健康与疾病临床医学研究中心儿童发育疾病研究教育部重点实验室儿童发育重大疾病国家国际科技合作基地儿童神经发育与认知障碍重庆市重点实验室重庆 400010 
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中文摘要:
      目的 观察不同浓度视黄酸(RA)对缺氧缺血性脑损伤(HIBD)后神经修复及PI3K/Akt信号通路的影响。 方法 将原代培养的海马神经干细胞分为对照组、模型组、(0.5、1、5、10、50 μmol/L)RA组及RA(5 μmol/L)+PI3K抑制剂组,在培养第5天时各RA组及RA+PI3K抑制剂组分别给予相应浓度的RA干预,在培养第6天时模型组、各RA组及RA+PI3K抑制剂组均进行细胞氧糖剥夺(OGD)处理,RA+PI3K抑制剂组于OGD处理前2 h给予PI3K抑制剂LY294002干预。在OGD损伤后12 h、24 h及48 h时分别采用CCK-8法检测各组细胞存活率,于OGD损伤后24 h时采用RT-PCR法和Western blot法检测各组细胞RARα、PI3K、Akt、β-catenin、Cyclin D1蛋白及mRNA表达水平。 结果 在OGD损伤后24 h、48 h时5 μmol/L RA组的吸光度值(OD)均显著高于模型组水平(P<0.05),故本研究认为5 μmol/L RA对神经损伤的修复作用较显著。在OGD损伤后24 h时模型组细胞存活率显著低于5 μmol/L RA组,RA+PI3K抑制剂组细胞存活率亦显著低于5 μmol/L RA组(P<0.05)。进一步分析发现,5 μmol/L RA组RARα、PI3K、Cyclin D1蛋白及mRNA表达水平均较模型组显著升高(P<0.05);10 μmol/L RA组β-catenin蛋白及mRNA表达水平亦显著高于模型组(P<0.05);RA+PI3K抑制剂组RARα、PI3K、Akt、β-catenin、Cyclin D1蛋白及mRNA表达水平均较5 μmol/L RA组显著降低(P<0.05)。 结论 适宜浓度的RA干预可通过上调RARα表达,激活PI3K/Akt信号通路及下游Cyclin D1信号分子,从而有效促进OGD损伤后海马神经干细胞的增殖及修复进程。
英文摘要:
      Objective To observe any effect of retinoic acid (RA) concentration on nerve repair and PI3K/Akt signaling after hypoxic-ischemic brain damage (HIBD). Methods Primary cultured hippocampal neural stem cells were randomly divided into a control group, 0.5, 1, 5, 10 and 50μmol/L RA model groups and 5μmol/L RA+PI3K inhibitor group. The RA groups and the RA+PI3K inhibitor group were given those treatments at the appropriate concentrations on the 5th day of culture, and then all except the control group underwent cellular oxygen and glucose deprivation (OGD) on the following day. The RA+PI3K inhibitor group was given PI3K inhibitor LY294002 2h before the OGD treatment. The cell viability of each group was detected using the CCK8 method at 12, 24 and 48 hours after the start of the OGD. Twenty-four hours later, the expression levels of RARα, PI3K, Akt, β-catenin, cyclin D1 protein and mRNA were detected using a reverse-transcription-polymerase chain reaction and western blotting. Results The OD value of the 5μmol/L RA group was significantly higher than that of the model group 24 and 48h after the OGD, suggesting significant nerve injury repair. Also, 24h after the OGD the cell viability in the model and RA+PI3K inhibitor groups was significantly lower than in the 5μmol/L RA group. The expressions of RARα, PI3K, cyclin D1 protein and mRNA in the 5μmol/L RA group were significantly higher than in the model group, and those of β-catenin protein and mRNA in the 10μmol/L RA group were also significantly higher than in the model group. RARα, PI3K, Akt, β-catenin, cyclin D1 protein and mRNA in the RA+PI3K inhibitor group were significantly lower than in the 5μmol/L RA group. Conclusions RA of appropriate concentration can up-regulate RARα expression and activate PI3K/Akt signaling and its downstream cyclin D1, thereby effectively promoting the proliferation and repair of hippocampal stem cells after OGD.
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