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他莫昔芬可减少大鼠脊髓损伤后炎症细胞浸润、细胞凋亡,并抑制IKK/NF-κB通路。

Tamoxifen reduces infiltration of inflammatory cells, apoptosis and inhibits IKK/NF-kB pathway after spinal cord injury in rats.

作者信息

Wei Hong-Yu, Ma Xiao

机构信息

Department of Spinal Surgery, China-Japan Friendship Hospital, Beijing, 100029, China.

出版信息

Neurol Sci. 2014 Nov;35(11):1763-8. doi: 10.1007/s10072-014-1828-z. Epub 2014 May 30.

DOI:10.1007/s10072-014-1828-z
PMID:24873902
Abstract

In this study, neuroprotective effect of tamoxifen has been explored in spinal cord injury (SCI) in rats by examining factors influencing IKK/NF-kB pathway in SCI in rats. It has been shown in several studies that IKK/NF-kB signaling pathway plays a key role in pathophysiology of SCI. In this study, three groups of rats (n = 17 each) were selected that included, tamoxifen group (here tamoxifen was injected after SCI in rats), SCI group (here only dimethylsulfoxide was administered after inducing SCI in rats) and sham group (here only laminectomy was performed). The effect of tamoxifen (5 mg/kg) on various factors responsible for activation of IKK/NF-kB signaling pathway including NF-kB p65, phosphorylated I-kBα was studied through Western blotting as well as densitometry. The examination of expression of active caspase-3 and myeloperoxidase activity was also carried out through Western blot analysis and densitometry. A comparison of three groups of rats showed that administration of tamoxifen significantly reduced the expression of NF-kB p65 and phosphorylated I-kBα (P < 0.05) compared to control. It also attenuated the expression of active caspase-3 resulting in the reduction of apoptosis, and infiltration of leukocytes to the injury site was also greatly reduced in the group where tamoxifen was administered. Statistical analysis through SPSS 13.0 software showed a significant decrease in the expression of inflammatory factors in groups where tamoxifen was administered. We conclude that tamoxifen possesses the potential neuroprotective effects that can be explored further for future therapeutic techniques in treating spinal cord injuries.

摘要

在本研究中,通过检测影响大鼠脊髓损伤(SCI)中IKK/NF-κB信号通路的因素,探讨了他莫昔芬对大鼠脊髓损伤的神经保护作用。多项研究表明,IKK/NF-κB信号通路在脊髓损伤的病理生理学中起关键作用。在本研究中,选取三组大鼠(每组n = 17),包括他莫昔芬组(大鼠脊髓损伤后注射他莫昔芬)、脊髓损伤组(大鼠诱导脊髓损伤后仅给予二甲基亚砜)和假手术组(仅进行椎板切除术)。通过蛋白质免疫印迹法以及光密度测定法研究了他莫昔芬(5 mg/kg)对负责激活IKK/NF-κB信号通路的各种因素的影响,这些因素包括NF-κB p65、磷酸化的I-κBα。还通过蛋白质免疫印迹分析和光密度测定法检测了活性半胱天冬酶-3的表达和髓过氧化物酶活性。三组大鼠的比较表明,与对照组相比,给予他莫昔芬显著降低了NF-κB p65和磷酸化I-κBα的表达(P < 0.05)。它还减弱了活性半胱天冬酶-3的表达,从而减少了细胞凋亡,并且在给予他莫昔芬的组中,白细胞向损伤部位的浸润也大大减少。通过SPSS 13.0软件进行的统计分析表明,给予他莫昔芬的组中炎症因子的表达显著降低。我们得出结论,他莫昔芬具有潜在的神经保护作用,可在未来治疗脊髓损伤的治疗技术中进一步探索。

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本文引用的文献

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Neurosci Lett. 2012 Mar 5;511(1):28-32. doi: 10.1016/j.neulet.2012.01.030. Epub 2012 Jan 24.
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