膜表面活性剂泊洛沙姆188抗神经兴奋性毒性的作用及机制  

Neuroprotective effects of the surfactant poloxamer 188 in excitotoxicity and underlying mechanisms

作　　者：李春华[1,2] 王燕[2] 秦正红[2] 

机构地区：[1]苏州大学附属第一医院药剂科,江苏苏州215006 [2]苏州大学医学部药学院药理学系 苏州市衰老与神经疾病实验室,江苏苏州215123

出　　处：《中国药理学通报》2010年第11期1418-1424,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30772560,30930035)

摘　　要：目的研究泊洛沙姆188(poloxamer188,P188)在NM-DA受体介导的神经兴奋性毒性中的作用及其机制。方法采用脑立体定位纹状体内注射喹啉酸(quinolinic acid,QA),建立NMDA受体介导的大鼠神经兴奋性毒性模型,尼式染色法和细胞计数法观察P188舌下静脉预防给药对模型大鼠纹状体神经元的保护作用。Western blot法检测P188对模型大鼠纹状体IκB-α、DRAM和LAMP-2蛋白表达的影响。结果尼式染色和细胞计数结果显示P188给药组与QA模型组相比,损伤面积明显减小(P<0.01),神经元数目明显增加(P<0.01)。Western blot结果显示大鼠纹状体注射QA后,模型大鼠纹状体内IκB-α蛋白水平明显降低,而DRAM和LAMP-2蛋白表达增加,P188预给药可抑制QA引起的大鼠纹状体中IκB-α,DRAM和LAMP-2蛋白表达的变化。结论 P188有拮抗神经兴奋性毒性的作用,这种神经保护作用可能与抑制IkB-α降解防止NF-κB激活和抑制自噬活性有关。Aim To study the neuroprotective effects and mechanisms of the surfactant poloxamer 188 in excitotoxicity mediated by NMDA receptors.Methods Rat excitotoxic model was produced with stereotaxic administration of quinolinic acid （QA） into unilateral striatum.The neuroprotective effects of P188 were de-tected with Nissl staining and unbiased cell counting.Protein levels of IκB-α,DRAM and LAMP-2 in striatum were determined by Western blot analysis.Rats were pre-treated with sublingual vein injection of P188 10 min prior to intrastriatal injection of QA.Results Nissl staining and cell counting revealed that pre-treatment with P188 significantly reduced the loss of striatal neurons and significantly reduced lesion size induced by QA（P0.01）.Western blot analysis revealed that there was a decrease in IκB-α protein level,while there were increases in the protein levels of DRAM and LAMP-2.Pre-treatment with P188 inhibited QA-induced changes in IκB-α,DRAM,and LAMP-2 （P 0.01）.Conclusion P188 has neuroprotective actions against QA-induced striatal damage and neuronal loss,Which may involve inhibiting IκB-α degradation and autophagy activation.

关 键 词：泊洛沙姆188 喹啉酸 兴奋性毒性 IΚB-Α DRAM LAMP-2 

分 类 号：R-332[医药卫生] R322.81