Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin
Amelioration of experimental allergic encephalomyelitis in Lewis rats by lovastatin
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DOI：
10.1016/s0304-3940(99)00414-0
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发表时间：
1999-07-09
影响因子：
2.5
通讯作者：
Singh, I
中科院分区：
文献类型：
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作者：
Stanislaus, R;Pahan, K;Singh, I
促炎细胞因子和诱导型一氧化氮合酶（iNOS）参与多发性硬化（MS）动物模型实验性变态反应性脑脊髓炎（EAE）的发病机制。我们先前已经报道了洛伐他汀（Pahan，K.，酋长F.G.，Namboodiri，A.和辛格，我，洛伐他汀和苯乙酸抑制大鼠原代星形胶质细胞、小胶质细胞和巨噬细胞中一氧化氮合酶和细胞因子的诱导。J. Clin. Invest.，100（1997）2671-2679。），甲羟戊酸途径的抑制剂，抑制大鼠原代神经胶质细胞（星形胶质细胞和小胶质细胞）和巨噬细胞中iNOS和促炎细胞因子的表达。本研究强调了洛伐他汀在改善EAE大鼠中枢神经系统神经炎性疾病过程中的治疗重要性。免疫组织化学结果显示，与对照动物相比，急性EAE大鼠脑中iNOS、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的表达程度更高。给予洛伐他汀可抑制EAE大鼠CNS中iNOS、TNF-α和IFN-γ的表达，并改善EAE的临床体征，表明该化合物可能具有治疗神经炎性疾病（如MS）的治疗潜力。（C）1999 Elsevier Science爱尔兰Ltd.保留所有权利。
Proinflammatory cytokines and inducible nitric oxide synthase (iNOS) are involved in the pathogenesis of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). We have previously reported that lovastatin (Pahan, K., Sheikh., F.G., Namboodiri, A. and Singh, I., Lovastatin and Phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia and macrophages. J. Clin. Invest., 100 (1997) 2671-2679.), an inhibitor of the mevalonate pathway, inhibits the expression of iNOS and proinflammatory cytokines in rat primary glial cells (astroglia and microglia) and macrophages. The present study underlines the therapeutic importance of lovastatin in ameliorating the neuroinflammatory disease process in the central nervous system of EAE rats. Immunohistochemical results show a higher degree of expression of iNOS, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in brains of rats with acute monophasic EAE relative to the control animals. Administration of lovastatin inhibited the expression of iNOS, TNF-alpha and IFN-gamma in the CNS of EAE rats and improved the clinical signs of EAE suggesting that this compound may have therapeutic potential in the treatment of neuroinflammatory diseases like MS. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.