Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.

IF 2.9 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Prostaglandins, leukotrienes, and essential fatty acids Pub Date : 2003-10-01 DOI:10.1016/s0952-3278(03)00109-1

Katsuhiko Nakai, Yoshifumi Takenobu, Hideyuki Takimizu, Shinji Akimaru, Hidenori Ito, Hitoshi Maegawa, Martin Marsala, Nobuo Katsube

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引用次数: 8

Abstract

An orally active prostaglandin E1 analogue, OP-1206 alpha-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis. To determine whether the OP-1206 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-CD treatment alone after chronic spinal stenosis in the rat. Spinal stenosis was induced by placing two pieces of silicon rubber strips in the lumbar (L4 and L6) epidural space of rats. After surgery, walking function was measured using a treadmill apparatus and SCBF was measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from the day 3 post-surgery. OP-1206 alpha-CD elicited a significant improvement of walking dysfunction on days 7 and 14 post-surgery and significantly increased spinal cord blood flow on day 15, whereas walking dysfunction and SCBF of rats treated with loxoprofen-Na alone remained unchanged. Combined treatment of OP-1206 alpha-CD with loxoprofen-Na did not provide additive therapeutical effect. These results suggest that a significant improvement seen after OP-1206 alpha-CD treatment is primarily mediated by improvement of the local spinal cord blood flow. This effect is not ameliorated or potentiated by a combined treatment with loxoprofen-Na.

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口服OP-1206 α - cd联合loxoprofen-Na对神经性间歇性跛行模型大鼠行走功能障碍的影响。

口服活性前列腺素E1类似物OP-1206 α - cd改善大鼠椎管狭窄模型的行走功能障碍。Loxoprofen-Na是一种非甾体抗炎药，用于缓解腰椎管狭窄患者的慢性疼痛。探讨OP-1206 α - cd联合loxoprofen-Na对慢性椎管狭窄大鼠行走功能障碍和脊髓血流(SCBF)的治疗效果是否优于OP-1206 α - cd单独治疗。在大鼠腰(L4和L6)硬膜外间隙置入两根硅橡胶条诱导椎管狭窄。术后用跑步机测量行走功能，用激光多普勒血流仪测量SCBF。从术后第3天开始，每天口服药物2次，持续11天。OP-1206 α - cd在术后第7天和第14天显著改善了大鼠的行走功能障碍，并在第15天显著增加了脊髓血流量，而loxoprofen-Na单独治疗的大鼠的行走功能障碍和SCBF保持不变。OP-1206 α - cd与loxoprofen-Na联合治疗无附加疗效。这些结果表明，OP-1206 α - cd治疗后的显著改善主要是由局部脊髓血流的改善介导的。与洛索洛芬钠联合治疗不能改善或增强这种效果。

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来源期刊

Prostaglandins, leukotrienes, and essential fatty acids 医学-内分泌学与代谢

CiteScore

6.40

自引率

6.70%

发文量

审稿时长

13.2 weeks

期刊介绍： The role of lipids, including essential fatty acids and their prostaglandin, leukotriene and other derivatives, is now evident in almost all areas of biomedical science. Cell membrane behaviour and cell signalling in all tissues are highly dependent on the lipid constituents of cells. Prostaglandins, Leukotrienes & Essential Fatty Acids aims to cover all aspects of the roles of lipids in cellular, organ and whole organism function, and places a particular emphasis on human studies. Papers concerning all medical specialties are published. Much of the material is particularly relevant to the development of novel treatments for disease.