| 王少朋,王 茹,李丹丹,马 芮,赵弘轶,黄勇华,迟丽屹.褪黑素对慢性脑低灌注大鼠海马齿状回区神经再生的影响[J].,2019,19(7):1251-1256 |
| 褪黑素对慢性脑低灌注大鼠海马齿状回区神经再生的影响 |
| Effects of Melatonin on Neuron Proliferation in Dentate Gyrus Area of Hippocampal of Rats with Chronic Cerebral Hypoperfusion |
| 投稿时间：2018-12-17 修订日期：2019-01-21 |
| DOI：10.13241/j.cnki.pmb.2019.07.010 |
| 中文关键词: 褪黑素 海马 脑低灌注 神经再生 |
| 英文关键词: Melatonin Hippocampus Cerebral hypoperfusion Neurogenesis |
| 基金项目:解放军空军后勤科研基金项目（CKJ17J019） |
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| 中文摘要: |
| 摘要 目的：研究褪黑素在慢性脑低灌注（Chronic Cerebral Hypoperfusion，CCH）大鼠模型中对神经再生的作用及机制。方法：使用双侧颈总动脉结扎法（bilateral common carotid artery occlusion，BCCAO）制备大鼠CCH模型，80只雄性的SD大鼠随机分为4组，每组20只：生理盐水治疗假手术组（Sham组）、生理盐水治疗模型组（BCCAO组）、褪黑素（5 mg/kg）治疗模型组（MT1组）、褪黑素（10 mg/kg）治疗模型组（MT2组）。连续腹腔注射褪黑素或生理盐水共4周。利用挖掘实验评估大鼠行为学；使用HE染色观察神经细胞变性及坏死；采取尼氏染色法观察大鼠海马齿状回区神经元损伤情况；利用免疫荧光法测定神经元特异核蛋白（NeuN）、胶质纤维酸性蛋白（Ki67）、双皮质素（DCX）的表达；利用Western Blot法测定大鼠海马区脑源性神经营养因子（BDNF）、酪氨酸激酶B受体(TrkB)含量的表达。结果：和Sham组相比，BCCAO组大鼠挖掘能力明显下降（P<0.01），HE和尼氏染色出现神经细胞大量坏死、数量减少，NeuN阳性细胞数增加（P<0.01）、Ki67/DCX阳性细胞数无明显增加（P>0.05），BDNF、TrkB蛋白含量明显低于假手术组（P<0.01）。与BCCAO组相比，MT1组和MT2组大鼠挖掘能力均明显改善（P<0.01），HE和尼氏染色显示神经元存活数量增加，MT1组NeuN阳性细胞数增加（P<0.05）、Ki67/DCX阳性细胞数增加（P<0.05），MT2组NeuN、Ki67/DCX阳性细胞数明显增加（P<0.01），MT1组及MT2组BDNF、TrkB蛋白含量明显增加（P<0.01）。结论：褪黑素促进了CCH大鼠海马齿状回区神经再生和行为学的改变，其机制可能与激活BDNF-TrkB信号转导通路有关。 |
| 英文摘要: |
| ABSTRACT Objective: Investigate the role and mechanism of melatonin on neuron regeneration in a rat model of Chronic Cerebral Hypoperfusion(CCH). Methods: Rat CCH model was made by bilateral common carotid artery occlusion (BCCAO). Eighty male Sprague-Dawley rats were randomly assigned to 4 groups(n=20): the sham operation group（Sham group）, the BCCAO group（BCCAO group）, the BCCAO with melatonin (5 mg/kg) treatment group（MT1 group）, and the BCCAO with melatonin (10 mg/kg) treatment group（MT2 group）. Continuous administration of melatonin or saline were used for 4 weeks. The behavioral research of rats was evalu- ated by burrowing experiment and use HE staining to observe neuronal degeneration and necrosis. The neuronal damage on the dentate gyrus of rat hippocampus was observed by Nissl staining. The expression of neuron-specific nuclear protein (NeuN), glial fibrillary acidic protein (Ki67)and double cortisol (DCX) were determined by immunofluorescence. Western Blot method was used to determine the ex- pression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B receptor (TrkB) in rat hippocampus. Results: Compared with Sham group, the burrowing ability of rats in BCCAO group was significantly decreased（P<0.01）. The number of necrotic cells and neurons in HE and Nissl staining were decreased significantly, and the number of NeuN and Ki67/DCX positive cells did not increase significantly (P>0.05). The protein content of BDNFwas decreased(P<0.01) and TrkB was significantly lower than that of the sham oper- ation group (P<0.01). Compared with the BCCAO group, the burrowing ability of the rats in the MT1 group and the MT2 group was sig- nificantly improved(P<0.01). HE and Nissl staining showed an increase in the number of neurons surviving, and the number of NeuN was increased（P<0.05） and Ki67/DCX positive cells in the MT1 group was increased（P<0.01）. The number of NeuN and Ki67/DCX posi- tive cells in MT2 group was increased significantly (P<0.01), and the content of BDNF and TrkB protein in MT1 group and MT2 group was increased significantly (P<0.01). Conclusion: Melatonin promoted neuronal regeneration and behavioral changes in the dentate gyrus of CCH rats, and its mechanism may be related to activation of BDNF-TrkB signal transduction pathway. |
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