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醋酸亮丙瑞林,一种 GnRH 激动剂,可改善实验性自身免疫性脑脊髓炎:多发性硬化症的一种可能疗法。

Leuprolide acetate, a GnRH agonist, improves experimental autoimmune encephalomyelitis: a possible therapy for multiple sclerosis.

机构信息

Laboratory of Neurophysiology, Department of Physiology and Pharmacology, Centro de Ciencias Básicas, Universidad Autónoma de Aguascalientes, Av. Universidad 940, C.P. 20131 Aguascalientes, Mexico.

出版信息

Neurochem Res. 2012 Oct;37(10):2190-7. doi: 10.1007/s11064-012-0842-x. Epub 2012 Jul 26.

Abstract

Gonadotrophin-releasing hormone (GnRH), a well known hypothalamic neuropeptide, has been reported to possess neurotrophic properties. Leuprolide acetate, a synthetic analogue of GnRH is considered to be a very safe and tolerable drug and it has been used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. The present study was designed to determine whether Leuprolide acetate administration, exerts neurotrophic effects on clinical signs, body weight gain, neurofilaments (NFs) and myelin basic protein (MBP) expression, axonal morphometry and cell infiltration in spinal cord of experimental autoimmune encephalomyelitis (EAE) rats. In this work, we have found that Leuprolide acetate treatment decreases the severity of clinical signs of locomotion, induces a significantly greater body weight gain, increases the MBP and NFs expression, axonal area and cell infiltration in EAE animals. These results suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis.

摘要

促性腺激素释放激素(GnRH),一种众所周知的下丘脑神经肽,已被报道具有神经营养特性。醋酸亮丙瑞林是 GnRH 的合成类似物,被认为是一种非常安全和耐受良好的药物,已被用于多种临床应用,包括治疗前列腺癌、子宫内膜异位症、子宫肌瘤、中枢性性早熟和体外受精技术。本研究旨在确定醋酸亮丙瑞林给药是否对实验性自身免疫性脑脊髓炎(EAE)大鼠的临床症状、体重增加、神经丝(NFs)和髓鞘碱性蛋白(MBP)表达、轴突形态计量和细胞浸润产生神经营养作用。在这项工作中,我们发现醋酸亮丙瑞林治疗可降低运动功能障碍的临床症状严重程度,显著增加体重增加,增加 EAE 动物的 MBP 和 NFs 表达、轴突面积和细胞浸润。这些结果表明,这种激动剂可作为多发性硬化症的潜在治疗方法。

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