首页> 外文期刊>Current therapeutic research, clinical and experimental. >N-Acetyl-L-Cysteine Attenuates Ischemia/Reperfusion Injury-Induced Allodynia and N-Methyl-D-Aspartate Receptor Activation in Rats
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N-Acetyl-L-Cysteine Attenuates Ischemia/Reperfusion Injury-Induced Allodynia and N-Methyl-D-Aspartate Receptor Activation in Rats

机译:N-乙酰基-L-半胱氨酸减轻大鼠缺血/再灌注损伤引起的异常性疼痛和N-甲基-D-天冬氨酸受体活化

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BACKGROUND: Although reactive oxygen species (ROS) are believed to be involved in pathogenic mechanisms that underlie complex regional pain syndrome type I (CRPS-I), the role of ROS in the central mechanism of CRPS is not fully understood.OBJECTIVE: In this study we investigated whether ROS scavenger N-acetyl-L-cysteine (NAC) was capable of attenuating mechanical allodynia and whether pain was decreased through modulating N-methyl-D-aspartate (NMDA) receptor activation in a chronic postischemia pain (CPIP) animal model that mimics the symptoms of CRPS-I.METHODS: Thirty male Sprague-Dawley rats were randomly allocated to 5 different groups: (1) sham rats and CPIP rats treated with (2) vehicle; (3) NAC 30 mg/kg; (4) NAC 100 mg/kg; and (5) NAC 300 mg/kg intraperitoneally at 15 minutes before reperfusion. CPIP was generated after a 3-hour ischemia/reperfusion injury on the hind limb using a tight fitting O-ring. Then, mechanical paw-withdrawal thresholds to von Frey stimuli were assessed before ischemia (baseline), at 4 hours; 1, 3, and 5 days; and 1, 2, 3, and 4 weeks after reperfusion. Another set of 5 animal groups in the same categories was used to determine phosphorylated NMDA receptor 1 subunit (pNRl) immunoreactivity in the ipsilateral L4/6 spinal cord at 3 days after reperfusion.RESULTS: The sham group showed no significant difference in pain thresholds over 4 weeks. With NAC treatment, the pain thresholds measured after reperfusion increased significantly, and this increase lasted 4 weeks after reperfusion compared with the vehicle group (P < 0.01 on the ipsilateral side and P < 0.05 on the contralateral side). The relative density of pNRl at 3 days after reperfusion in NAC-treated rats decreased significantly compared with that of the vehicle group (all, P < 0.001). The NAC dose was significantly correlated not only with paw-withdrawal threshold (p = 0.979; P < 0.001) but also with the relative density of pNRl (p = -0.875; P < 0.001).CONCLUSIONS: NAC, adm...
机译:背景:尽管人们认为活性氧(ROS)参与了复杂的I型区域性疼痛综合征(CRPS-I)的致病机制,但尚未完全了解ROS在CRPS中心机制中的作用。我们研究了在慢性缺血后疼痛(CPIP)动物中ROS清除剂N-乙酰-L-半胱氨酸(NAC)是否能够减轻机械性异常性疼痛以及是否通过调节N-甲基-D-天冬氨酸(NMDA)受体激活来减轻疼痛方法:将30只雄性Sprague-Dawley大鼠随机分为5组:(1)假大鼠和CPIP大鼠(2)载体; (3)NAC 30毫克/千克; (4)NAC 100毫克/千克; (5)在再灌注前15分钟腹腔注射NAC 300 mg / kg。使用紧紧的O形圈在后肢进行3小时的缺血/再灌注损伤后产生CPIP。然后,在缺血前(基线)4小时,评估冯弗雷刺激的机械爪退缩阈值。 1、3和5天;再灌注后的1、2、3和4周。在再灌注后3天,使用同一组的另一组5个动物组来确定同侧L4 / 6脊髓中磷酸化的NMDA受体1亚基(pNR1)的免疫反应性。 4个星期使用NAC治疗后,再灌注后测得的疼痛阈值显着增加,并且与媒介物组相比,这种增加持续了再灌注后4周(同侧P <0.01,对侧P <0.05)。与溶媒组相比,NAC处理的大鼠在再灌注后3天时pNR1的相对密度显着降低(所有,P <0.001)。 NAC剂量不仅与爪退出阈值(p = 0.979; P <0.001)显着相关,而且与pNR1的相对密度(p = -0.875; P <0.001)显着相关。结论:NAC,adm ...

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