| Nrf2通路活化在胆红素脑病新生大鼠海马神经元损伤中的作用 |
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| 引用本文： | 刘龙宾,唐丽霞,林新祝,李雅丹. Nrf2通路活化在胆红素脑病新生大鼠海马神经元损伤中的作用[J]. 四川大学学报(医学版), 2021, 52(6): 960-965. DOI: 10.12182/20211160502 |
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| 作者姓名： | 刘龙宾 唐丽霞 林新祝 李雅丹 |
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| 作者单位： | 厦门大学附属妇女儿童医院(厦门市妇幼保健院) 新生儿科 厦门 361003 |
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| 基金项目： | 厦门市科技计划重大专项基金项目（No. 3502Z20171006）资助 |
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| 摘 要： | 目的 探讨核因子NF-E2相关因子（nuclear factor-erythroid 2-related factor, Nrf2）通路活化对胆红素脑病新生大鼠海马神经元损伤的影响。 方法 将新生SD大鼠随机分为对照组、模型组和Nrf2激活剂特丁基对苯二酚（tert-Butylhydroquinone, TBHQ）组，每组20只。经小脑延髓池注射胆红素溶液，建立新生大鼠胆红素脑病模型，观察大鼠神经行为变化，并测定脑组织含水量；采用尼式（Nissl）染色观察海马神经元损伤；TUNEL染色观察海马神经元凋亡情况；比色法检测海马组织Caspase-3活性；化学法检测海马组织丙二醛（MDA）、还原型谷胱甘肽（GSH）含量和超氧化物歧化酶（SOD）活性；qRT-PCR和Western blot检测海马组织Nrf2和血红素氧合酶1（heme oxygenase-l, HO-1）mRNA和蛋白表达水平。 结果 小脑延髓池注射胆红素后模型组和TBHQ组幼鼠出现不同程度神经异常行为表现，而对照组幼鼠无明显神经异常行为。与对照组比较，模型组幼鼠神经元损伤严重，脑组织含水量以及海马神经元凋亡水平、Caspase-3活性以及MDA含量升高（P<0.01），而SOD活性、GSH含量以及Nrf2 和HO-1 mRNA和蛋白表达水平降低（P<0.05）；与模型组比较，TBHQ组幼鼠神经元损伤得到改善，脑组织含水量、海马神经元凋亡水平、Caspase-3活性以及MDA含量均降低（P<0.01），而SOD活性、GSH含量以及Nrf2 和HO-1 mRNA和蛋白表达水平升高（P<0.05）。 结论 Nrf2通路活化能改善胆红素脑病新生大鼠海马神经元损伤，抑制神经元凋亡和机体氧化反应。
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| 关 键 词： | 胆红素脑病 海马神经元损伤 Nrf2通路 细胞凋亡 |
| 收稿时间： | 2020-09-18 |
The Role of Nrf2 Pathway Activation in Hippocampal Neuron Injury of Neonatal Rats with Bilirubin Encephalopathy |
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| LIU Long-bin,TANG Li-xia,LIN Xin-zhu,LI Ya-dan. The Role of Nrf2 Pathway Activation in Hippocampal Neuron Injury of Neonatal Rats with Bilirubin Encephalopathy[J]. Journal of Sichuan University. Medical science edition, 2021, 52(6): 960-965. DOI: 10.12182/20211160502 |
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| Authors: | LIU Long-bin TANG Li-xia LIN Xin-zhu LI Ya-dan |
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| Affiliation: | Department of Neonatology, Affiliated Women and Children’s Hospital of Xiamen University/Xiamen City Women and Children’s Hospital, Xiamen 361003, China |
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| Abstract: | Objective To explore the effect of nuclear factor-erythroid 2-related factor (Nrf2) pathway activation on hippocampal neuron damage in neonatal rats with bilirubin encephalopathy. Methods Neonatal rats were randomly assigned to a control group (Control), a model group (Model) and an Nrf2 activator TBHQ (tert-Butylhydroquinone) group (TBHQ), with 20 rats in each group. Bilirubin solution was injected through the cerebellomedullary cistern to establish the neonatal rat model of bilirubin encephalopathy. Neurobehavioral changes were observed in rats and the water content of the brain tissue was measured. Nissl staining was done to observe the damage of hippocampal neurons. TUNEL staining was used to observe the apoptosis of hippocampal neurons. Colorimetric analysis was done to determine the Caspase-3 activity in the hippocampus. The content of malondialdehyde (MDA) and reduced glutathione (GSH) and the activity of superoxide dismutase (SOD) in the hippocampus were examined by chemical analysis. qRT-PCR and Western blot were done to measure the expression of Nrf2 and heme oxygenase-l (HO-1) mRNA and proteins in the hippocampus. Results After injection of bilirubin into the cerebellomedullary cistern, the young rats in the Model group and the TBHQ group showed different degrees of neurological abnormalities, while those in the control group showed no significant neurobehavioral abnormalities. Compared with the Control group, the Model group had severe neuronal damage, and the water content of brain tissue, the apoptosis of hippocampal neurons, the activity of Caspase-3 and the content of MDA content significantly increased (P<0.01), while the SOD activity, GSH content, the expression of Nrf2 and HO-1 mRNA and proteins significantly decreased (P<0.05). Compared with the Model group, neuronal damage was improved in the TBHQ group, and the water content of brain tissue, apoptosis of hippocampal neurons, activity of Caspase-3 and MDA content were all significantly reduced (P<0.01), while SOD activity, GSH content and the expression of Nrf2 and HO-1 mRNA and proteins were significantly increased (P<0.05). Conclusion Activation of the Nrf2 pathway can improve hippocampal neuronal damage in neonatal rats with bilirubin encephalopathy and inhibit neuronal apoptosis and the oxidation reaction. |
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