衣霉素海马内给药诱导海马神经元死亡的新现象与假说

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背景:海马内注射衣霉素和红藻氨酸均可诱导内质网应激介导海马神经元凋亡,但两者大有不同。目的:比较海马CA1区内注射红藻氨酸和衣霉素后不同时间段海马神经元的死亡情况。方法:将96只成年雄性昆明小白鼠随机分为PBS组、红藻氨酸组和衣霉素组,海马CA1区分别注射红藻氨酸、衣霉素和PBS。结果与结论:Fluoro-Jade B染色显示,红藻氨酸组小白鼠注射后2,3,4,5,6,8 h损伤侧出现海马神经元死亡明显。衣霉素组小白鼠注射后4 h损伤侧CA1区可见神经元明显死亡,对侧无明显死亡;衣霉素组小白鼠注射后5 h损伤侧CA1-3区未见神经元明显死亡,但对侧CA1-3区可见大量神经元死亡。免疫组化染色显示,衣霉素组小白鼠注射后4,5 h神经元死亡明显区域内磷酸化真核翻译起始因子2α的表达明显上调。结果提示海马内注射衣霉素后5 h出现海马神经元同侧给药对侧死亡的现象,是由于海马内注射衣霉素后随着药物浓度的扩散在4.0-5.0 h间神经元凋亡可能有一个由同侧向对侧迅速蔓延的过程,这是不同于红藻氨酸海马内注射诱导神经元死亡过程的又一新现象。 BACKGROUND: Both tunicamycin and kainic acid can induce endoplasmic reticulum stress-mediated apoptosis in hippocampal neurons, but the two are very different. OBJECTIVE: To compare the death of hippocampal neurons at different time points after injection of kainic acid and tunicamycin in hippocampal CA1 area. Methods: Ninety-six adult male Kunming mice were randomly divided into PBS group, kainic acid group and tunicamycin group. Kainic acid, tunicamycin and PBS were injected into CA1 area of ​​hippocampus respectively. RESULTS AND CONCLUSION: Fluoro-Jade B staining showed that neurons in hippocampal CA1 group showed obvious neuronal death at 2, 3, 4, 5, 6 and 8 h after injection. At 4 h after injection, the neurons in the tunicamycin group showed obvious neuronal death 4 h after injury and no significant contralateral dying. In the tunicamycin group, no significant neuronal death occurred in the caudal CA1-3 area 5 h after injection, Contralateral CA1-3 area shows a large number of neuronal death. Immunohistochemical staining showed that the expression of phosphorylated eukaryotic translation initiation factor 2α was obviously upregulated in the area of ​​obvious neuronal death 4,5 h after injection of tunicamycin in mice. The results suggest that hippocampal 5 hours after injection of tunicamycin hippocampal neurons ipsilateral side effects of death due to intramuscular injection of tunicamycin with the proliferation of drug concentration in the 4.0-5.0 h apoptosis between neurons There may be a rapid spread from the same side to the opposite side of the process, which is different from the kainic acid injection of hippocampal neurons death induced a new phenomenon.
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