Tetramethylpyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury
Tetramethylpyrazine protects spinal cord and reduces inflammation in a rat model of spinal cord ischemia-reperfusion injury
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DOI：
10.1016/j.jvs.2010.12.030
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发表时间：
2011-07-01
影响因子：
4.3
通讯作者：
Dang, Xiaoqian
中科院分区：
文献类型：
--
作者：
Fan, Lihong;Wang, Kunzheng;Dang, Xiaoqian
目的：炎症是缺血性卒中后急性期神经功能损害的重要因素，为脊髓缺血再灌注损伤的预防和治疗提供了一个潜在的靶点。川芎嗪（TMP）是从川芎中提取的纯化合物，广泛用于治疗缺血性脑卒中。本研究旨在深入了解TMP对脊髓缺血-再灌注损伤的抗炎作用机制。方法：采用球囊闭塞胸主动脉的方法，在雄性Sprague-Dawley大鼠中建立脊髓缺血模型。实验组（n = 30/组）包括假手术组、对照组（仅给予生理盐水）和TMP（30 mg/kg，阻断前30 min）。在再灌注后1、6、12、24和48小时通过Basso、Beattie和Bresnahan（BBB）评分评估神经功能。采用尼氏染色法观察组织学变化。使用氯化2，3，5-三苯基四唑染色分析脑体积。使用大鼠髓过氧化物酶（MPO）测定试剂盒测定髓过氧化物酶（MPO）活性。采用免疫组化、酶联免疫吸附试验（ELISA）和Western blotting检测白细胞介素（IL）-1 β、肿瘤坏死因子（TNF）-α、IL-10和核因子（NF）-κ B。与对照组相比，TMP组显示出显著改善的神经功能结局（P <0.05），减少梗死体积（42.3% vs 17.4%），减轻中性粒细胞浸润（0.35 vs 0.18 U/g）。TMP治疗降低了促炎细胞因子TNF-α的表达（28.62 vs 15.23 pg/mg蛋白）和IL-1 β（13.62 vs 8.24 pg/mg蛋白），上调抗炎细胞因子IL-10的表达结论：川芎嗪对脊髓缺血再灌注损伤具有神经保护作用。抗炎作用被认为是其作用机制之一。（J Vasc Surg 2011;54：192-200.）
Objective: Inflammation, which is known to be detrimental to the neurologic outcome during the acute phase after an ischemic stroke, provides a potential target for preventive or therapeutic approach for spinal cord ischemia-reperfusion injury. Tetramethylpyrazine (TMP), a pure compound derived from Ligusticum chuanxiong, is widely used in the treatment of ischemic stroke. The present study aimed to gain a deeper insight into the mechanism underlying the anti-inflammatory effects of TMP on spinal cord ischemia-reperfusion injury.Methods: Spinal cord ischemia was induced in male Sprague-Dawley rats by balloon occlusion of the thoracic aorta. The experimental groups (n = 30 per group) included sham operation, control (receiving only normal saline), and TMP (30 mg/kg, 30 minutes before occlusion). Neurologic function was assessed by the Basso, Beattie, and Bresnahan (BBB) score at 1, 6, 12, 24, and 48 hours after reperfusion. Histologic changes were studied using Nissl staining. Infarct volume was analyzed using 2,3,5-triphenyltetrazolium chloride staining. Myeloperoxidase (MPO) activity was determined by using a rat MPO assay kit. Interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-10 and nuclear factor (NF)-kappa B were examined with immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Western blotting.Results: Compared with the control group, the TMP group showed significantly improved neurologic outcome (P < .05), decreased infarct volume (42.3% vs 17.4%), and alleviated neutrophil infiltration (0.35 vs 0.18 U/g). TMP treatment reduced the expressions of proinflammatory cytokines TNF-alpha (28.62 vs 15.23 pg/mg protein) and IL-1 beta (13.62 vs 8.24 pg/mg protein), upregulated the expression of anti-inflammatory cytokine IL-10 (18.35 vs 31.26 pg/mg protein), and inhibited the activation of NF-kappa B (2.78 vs 1.22) in ischemic spinal cord.Conclusions: Treatment with TMP exerted a neuroprotective effect against spinal cord ischemia-reperfusion injury. The anti-inflammatory effect was believed to be one of the contributing mechanisms. (J Vasc Surg 2011;54:192-200.)