Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats
Attenuation of acute inflammatory response by atorvastatin after spinal cord injury in rats
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DOI：
10.1002/jnr.20345
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发表时间：
2005-02-01
影响因子：
4.2
通讯作者：
Singh, I
中科院分区：
文献类型：
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作者：
Pannu, R;Barbosa, E;Singh, I
脊髓损伤 (SCI) 是一种破坏性且复杂的临床病症，涉及促炎细胞因子和一氧化氮毒性，可产生可预测的进行性损伤模式，导致受影响部位的神经元损失、轴突破坏和脱髓鞘。促炎细胞因子和诱导型一氧化氮合酶 (iNOS) 在 SCI 病理恶化中的作用已有充分记录。我们之前曾报道过他汀类药物（3-羟基-3-甲基戊二酰[HMG]-CoA还原酶抑制剂）在多发性硬化症、实验性过敏性脑炎（EAE）动物模型中的抗炎特性和免疫调节活性。本研究旨在探讨阿托伐他汀（立普妥；ILP）治疗减轻 SCI 诱发病理的功效。免疫组织化学检测和实时PCR分析显示SCI后iNOS、肿瘤坏死因子α（TNFα）和白细胞介素1β（IL-1β）的表达增加。此外，损伤后 24 小时检测到神经元凋亡，随后 SCI 后 1 周，ED1 阳性炎症浸润、胶质纤维酸性蛋白 (GFAP) 阳性反应性星形胶质细胞和少突胶质细胞凋亡显着增加。 LP 治疗减弱了 SCI 诱导的 iNOS、TNFα 和 IL-1β 表达。 LP 还可以预防 SCI 引起的组织坏死、神经元和少突胶质细胞凋亡、脱髓鞘和反应性神经胶质增生。此外，接受 LP 治疗的大鼠在 SCI 后的运动评分量表上得分 (19.13 +/- 0.53) 比未治疗的大鼠 (9.04 +/- 1.22) 高得多。因此，本研究报告了阿托伐他汀对于治疗 SCI 相关病理和残疾的有益作用。 (C) 2004 Wiley-Liss, Inc.
Spinal cord injury (SCI) is a devastating and complex clinical condition involving proinflammatory cytokines and nitric oxide toxicity that produces a predictable pattern of progressive injury entailing neuronal loss, axonal destruction, and demyelination at the site of impact. The involvement of proinflammatory cytokines and inducible nitric oxide synthase (iNOS) in exacerbation of SCI pathology is well documented. We have reported previously the antiinflammatory properties and immunomodulatory activities of statins (3-hydroxy-3-methylglutaryl [HMG]-CoA reductase inhibitors) in the animal model of multiple sclerosis, experimental allergic encephalitis (EAE). The present study was undertaken to investigate the efficacy of atorvastatin (Lipitor; ILP) treatment in attenuating SCI-induced pathology. Immunohistochemical detection and real-time PCR analysis showed increased expression of iNOS, tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) after SCI. In addition, neuronal apoptosis was detected 24 hr after injury followed by a profound increase in ED1-positive inflammatory infiltrates, glial fibrillary acidic protein (GFAP)-positive reactive astrocytes, and oligodendrocyte apoptosis by 1 week after SCI relative to control. LP treatment attenuated the SCI-induced iNOS, TNFalpha, and IL-1beta expression. LP also provided protection against SCI-induced tissue necrosis, neuronal and oligodendrocyte apoptosis, demyelination, and reactive gliosis. Furthermore, rats treated with LP scored much higher on the locomotor rating scale after SCI (19.13 +/- 0.53) than did untreated rats (9.04 +/- 1.22). This study therefore reports the beneficial effect of atorvastatin for the treatment of SCI-related pathology and disability. (C) 2004 Wiley-Liss, Inc.