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白三烯B4受体拮抗剂SC - 41930对豚鼠实验性变应性脑脊髓炎(EAE)的影响。

Effect of the leukotriene B4 receptor antagonist, SC-41930, on experimental allergic encephalomyelitis (EAE) in the guinea pig.

作者信息

Fretland D J, Widomski D L, Shone R L, Levin S, Gaginella T S

机构信息

Department of Pathology, Searle Research and Development, Skokie, II 60077.

出版信息

Agents Actions. 1991 Sep;34(1-2):172-4. doi: 10.1007/BF01993269.

Abstract

The accepted model for the human demyelinating disease, multiple sclerosis (MS), is experimental allergic encephalomyelitis (EAE). We assessed the ability of SC-41930(7-[3(4-acetyl-3-methoxy-2-propyl-phenoxy)-propoxy]- 3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxyl acid), to modulate the symptoms of acute EAE generated in guinea pigs. Animals were pretreated with SC-41930 (20 mg/kg, i.p.) for two days followed by thrice-weekly maintenance. At day 52, a significant number of the SC-41930-treated animals were alive as compared to EAE alone. Control animals had an increase in body weight while EAE animals lost over 20% (p less than 0.5) of their body weight by day 18. SC-41930-treatment significantly reduced, but did not completely inhibit the cachectic response. The results indirectly implicate LTB4 in the pathogenesis of EAE. Agents that modify this model be useful in the treatment of human MS.

摘要

人类脱髓鞘疾病——多发性硬化症(MS)的公认模型是实验性自身免疫性脑脊髓炎(EAE)。我们评估了SC - 41930(7 - [3(4 - 乙酰基 - 3 - 甲氧基 - 2 - 丙基 - 苯氧基)-丙氧基]-3,4 - 二氢 - 8 - 丙基 - 2H - 1 - 苯并吡喃 - 2 - 羧酸)调节豚鼠急性EAE症状的能力。动物先用SC - 41930(20mg/kg,腹腔注射)预处理两天,然后每周维持三次。在第52天,与仅患EAE的动物相比,大量接受SC - 41930治疗的动物存活。对照动物体重增加,而EAE动物到第18天时体重减轻超过20%(p小于0.5)。SC - 41930治疗显著减轻,但未完全抑制恶病质反应。结果间接表明白三烯B4(LTB4)参与EAE的发病机制。改变该模型的药物可能对人类MS的治疗有用。

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