硫酸镁对大鼠血管性痴呆保护作用的研究
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摘要
背景与目的
血管性痴呆(vascular dementia，VD)是因脑血管疾病所致的智能及认知障碍的临床综合征，主要与缺血性脑血管病有关。随着世界人口老龄化，血管性痴呆的发病率逐年升高，已成为威胁人类，尤其是老龄人群健康的重要临床难题。如何采取措施减少神经元死亡，保护神经组织，减轻脑缺血后智能障碍，已成为当今研究的热点之一。
大量研究证明，痴呆患者的Mg~(2+)代谢存在一定异常，作为神经保护剂之一的硫酸镁(magnesium sulfate，MgSO_4)可通过各种途径阻滞或减轻神经元损伤，对痴呆具有预防和治疗作用。但是，对治疗用镁剂的浓度和确切的作用机制等还有待进一步求证。动物实验证实：脑损伤的神经细胞死亡形式与缺血缺氧的严重程度和持续时间有关。脑缺血引起的急性期神经元的死亡是以坏死为主，而继发性死亡或迟发性死亡则以凋亡为主。神经元型一氧化氮合酶(neuronal nitric oxide synthase，nNOS)在脑缺血时可催化产生一氧化氮(nitric oxide，NO)，这种NO对神经细胞有毒性作用。已有人提出Mg~(2+)可能通过调控细胞凋亡和nNOS活性，上调突触素表达，从而促进突触重塑，发挥其脑保护作用。
本实验通过“两血管阻断+硝普钠降压”法，即大鼠双侧颈总动脉反复夹闭并再通，同时腹腔注射硝普钠降低血压的方法建立VD大鼠模型，经鼠股静脉推注MgSO_4，用MG-2Y型迷宫比较大鼠学习记忆能力，光镜下观察细胞坏死情况变化，通过免疫组化方法观察大鼠脑海马突触素、nNOS阳性细胞表达，TUNEL法检测凋亡细胞，深入探讨MgSO_4对VD的疗效和作用机制及是否存在剂量依赖性，为临床应用MgSO_4治疗VD提供依据。
Background and Objective
Vascular dementia (VD) is an acquired impairment of cognitive function that caused by cerebral vascular diseases, mainly relate to the ischemic cerebrovascular diseases. With the aging population of the world, the incidence of vascular dementia rises year by year. It has already been a clinical difficult problem to threaten the health of mankind, especially the aged people. How can we take measures to reduce neuron death, protect the nerve cells, mitigate the intellectual obstacle after being ischemic have already become one of the focuses of current research.
A large amount of studies have proved that the metabolism of Mg~(2+) in vascular dementia patients is abnormal. As one of the neuron pharmaceutical protection, magnesium sulfate (MgSO_4) can block or mitigate the damage to the neurons through various methods, produce cooperative effect to dementia with other medicines. But it still needs to make a thorough study about the concentration of the pharmaceutical treatment of magnesium and precise function mechanism, etc. Animal's experiments verify: The death forms of neurons of brain injury relate to the severity and duration of the ischemia and anoxia. The acute death of neurons of brain relies mainly on necrosis, while delayed death relies mainly on apoptosis. Neuronal nitric oxide synthase (nNOS) can accelerate the production of the nitric oxide (NO) when there is ischemic in the brain. This kind of NO can do toxic to the nerve cells. Someone has
血管性痴呆(vascular dementia，VD)是因脑血管疾病所致的智能及认知障碍的临床综合征，主要与缺血性脑血管病有关。随着世界人口老龄化，血管性痴呆的发病率逐年升高，已成为威胁人类，尤其是老龄人群健康的重要临床难题。如何采取措施减少神经元死亡，保护神经组织，减轻脑缺血后智能障碍，已成为当今研究的热点之一。
大量研究证明，痴呆患者的Mg~(2+)代谢存在一定异常，作为神经保护剂之一的硫酸镁(magnesium sulfate，MgSO_4)可通过各种途径阻滞或减轻神经元损伤，对痴呆具有预防和治疗作用。但是，对治疗用镁剂的浓度和确切的作用机制等还有待进一步求证。动物实验证实：脑损伤的神经细胞死亡形式与缺血缺氧的严重程度和持续时间有关。脑缺血引起的急性期神经元的死亡是以坏死为主，而继发性死亡或迟发性死亡则以凋亡为主。神经元型一氧化氮合酶(neuronal nitric oxide synthase，nNOS)在脑缺血时可催化产生一氧化氮(nitric oxide，NO)，这种NO对神经细胞有毒性作用。已有人提出Mg~(2+)可能通过调控细胞凋亡和nNOS活性，上调突触素表达，从而促进突触重塑，发挥其脑保护作用。
本实验通过“两血管阻断+硝普钠降压”法，即大鼠双侧颈总动脉反复夹闭并再通，同时腹腔注射硝普钠降低血压的方法建立VD大鼠模型，经鼠股静脉推注MgSO_4，用MG-2Y型迷宫比较大鼠学习记忆能力，光镜下观察细胞坏死情况变化，通过免疫组化方法观察大鼠脑海马突触素、nNOS阳性细胞表达，TUNEL法检测凋亡细胞，深入探讨MgSO_4对VD的疗效和作用机制及是否存在剂量依赖性，为临床应用MgSO_4治疗VD提供依据。
Background and Objective
Vascular dementia (VD) is an acquired impairment of cognitive function that caused by cerebral vascular diseases, mainly relate to the ischemic cerebrovascular diseases. With the aging population of the world, the incidence of vascular dementia rises year by year. It has already been a clinical difficult problem to threaten the health of mankind, especially the aged people. How can we take measures to reduce neuron death, protect the nerve cells, mitigate the intellectual obstacle after being ischemic have already become one of the focuses of current research.
A large amount of studies have proved that the metabolism of Mg~(2+) in vascular dementia patients is abnormal. As one of the neuron pharmaceutical protection, magnesium sulfate (MgSO_4) can block or mitigate the damage to the neurons through various methods, produce cooperative effect to dementia with other medicines. But it still needs to make a thorough study about the concentration of the pharmaceutical treatment of magnesium and precise function mechanism, etc. Animal's experiments verify: The death forms of neurons of brain injury relate to the severity and duration of the ischemia and anoxia. The acute death of neurons of brain relies mainly on necrosis, while delayed death relies mainly on apoptosis. Neuronal nitric oxide synthase (nNOS) can accelerate the production of the nitric oxide (NO) when there is ischemic in the brain. This kind of NO can do toxic to the nerve cells. Someone has
引文
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