The protective effects of sphingolipid synthetic drug (L-PDMP) on apoptotic cell damage in cerebral infarction

鞘脂类合成药（L-PDMP）对脑梗死细胞凋亡损伤的保护作用

• 批准号: 11557108
• 负责人: NAKAGONI Tadayoshi
• 金额: $ 8.58万
• 依托单位: Teikyo Univ. School of Med.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557108/
• 关键词: Sphingolipid; Focal ischemia; L-PDMP; Behavior; MCA; Glucosylceramide; Sphingomyelin; hypothermia; delay neuronal death; ganglioside; 中大脳動脈閉塞モデル; グルコシルセラミド; 水迷路; セラミド; スフィンゴミエリン; ceramide; D-PDMP

L-PDMP (L-threo-l-phenyl-2-decanoylamino-3-morpholino-l-propanol) exhibits stimulatory effects on glycosphingolipid biosynthesis and its neurotrophic actions in cultured neuron. The effects of intraperitoneal administration of L-PDMP on sphingolipid metabolism and behavioral changes in the rat following permanent occlusion of the left middle cerebral artery (MCA) were investigated. The L-PDMP treatment induced increases in glucosylceramide (ganglioside precursor) and sphingomyelin (SM) levels in the ischemic cerebral cortex, and improved acquisition of memory and learning in the Morris water maze task. The pharmacological effects of L-PDMP have been proposed to have a significant activity on promoting cell survival and improving neural functions.

L-PDMP(L-threo-l-phenyl-2-decanoylamino-3-morpholino-l-propanol)对神经细胞神经鞘糖脂的生物合成及其神经营养作用具有促进作用。本文观察了大鼠大脑中动脉永久性闭塞后，腹腔注射L对鞘磷脂代谢及行为学改变的影响。L-PDMP治疗可使缺血大脑皮层神经节苷脂前体葡萄糖神经酰胺和鞘磷脂水平升高，并能改善小鼠在Morris水迷宫中的记忆和学习能力。L的药理作用被认为具有促进细胞存活和改善神经功能的显著作用。

项目成果

M.Kubota,M.Nakane,T.Nakagomi,A.Tamura,H.Hisaki,S.Shimasaki: "Mild hypothermia reduces the rate of metabolism of arachidonic acid following postischemic reperfusion"Brain Res. 779. 297-300 (1998)

M.Kubota、M.Nakane、T.Nakagomi、A.Tamura、H.Hisaki、S.Shimasaki：“轻度低温会降低缺血再灌注后花生四烯酸的代谢率”Brain Res。

M.Kubota,M.Nakane,T.Nakagomi,A.Tamura,H.Hisaki,S.Shimasaki: "Sphingomyelin changes in rat cerebral cortex during focal ischemia"Neurol Res. 18. 337-341 (1996)

M.Kubota，M.Nakane，T.Nakagomi，A.Tamura，H.Hisaki，S.Shimasaki：“局灶性缺血期间大鼠大脑皮层的鞘磷脂变化”Neurol Res。

Tamura A., Nakagomi T., Kanemitsu H., Mine K. et al.: "Cerebral acetylcholine levels and long-term spatial cognitive impairment following middle cerebral artery occlusion in rats"Japan J. Psychopharmacol. 19. 267-272 (1999)

Tamura A.、Nakagomi T.、Kanemitsu H.、Mine K. 等：“大鼠大脑中动脉闭塞后的脑乙酰胆碱水平和长期空间认知障碍”Japan J. Psychopharmacol。

M.Kubota,K.Narita,T.Nakagomi,A.Tamura,H.Hisaki,S.Shimasaki: "Fatty acid composition of the chronic subdural hematoma : with reference to its recurrence"J.Clin.Neuroscience. 5. 63-65 (1998)

M.Kubota，K.Narita，T.Nakagomi，A.Tamura，H.Hisaki，S.Shimasaki：“慢性硬膜下血肿的脂肪酸组成：与其复发有关”J.Clin.Neuroscience。

Kubota M, Nakane M, Nakagomi T, Tamura A, et al.: "Regional distribution of ethanolamine plasmalogen in the hippocampal CA1 and CA3 regions and cerebral cortex of the gerbil"Neuroscience Letter. 301. 175-178 (2001)

Kubota M、Nakane M、Nakagomi T、Tamura A 等人：“乙醇胺缩醛磷脂在沙鼠海马 CA1 和 CA3 区域以及大脑皮层中的区域分布”《神经科学快报》。