作 者 ：陈玉霞,肖农,林丽云,刘玲
期 刊 ：中国中药杂志 2009年 34卷 14期 页码：1852.
Keywords:cerebral ischemia, neural plasticity, brain-derived neurotrophic factor, apoptosis,
摘 要 ：目的：比较研究麻黄碱添加不同剂量纳洛酮后，干预大鼠脑缺血再灌注损伤后的神经可塑性变化，探讨麻黄碱配伍纳洛酮后能否产生协同作用，促进神经重塑的最适比例及其分子机制。方法：体重220～250 g SD大鼠192只，改良Koizumi线栓法建立左侧MCAO模型。随机分为8组：自然康复组（0.5 mL），麻黄碱治疗组(1.5 mg·kg-1·d-1)，小剂量纳洛酮治疗组(0.1 mg·kg-1·d-1)，中剂量纳洛酮治疗组(0.2 mg·kg-1·d-1)，高剂量纳洛酮治疗组(0.3 mg·kg-1·d-1)，麻黄碱+小剂量纳洛酮治疗组(1.5 mg·kg-1·d-1)，麻黄碱+中剂量纳洛酮治疗组(1.5 mg·kg-1·d-1)，麻黄碱+高剂量纳洛酮治疗组(1.5 mg·kg-1·d-1)，每天给药3次，腹腔注射。术后1，2，3，4周横木行走试验评定大鼠感觉运动整合功能恢复情况，免疫荧光方法检测缺血半球海马脑源性神经营养因子（BDNF）的表达，TUNEL法检测凋亡神经细胞数目。结果：横木行走试验，BDNF，TUNEL染色均显示纳络酮3个剂量组均无明显疗效，加上定量麻黄素后效果增加，且有量-效关系，其中麻黄碱+高剂量纳洛酮治疗组运动功能恢复最快，BDNF表达最好及缺血侧海马凋亡神经细胞最少，缺血损伤最轻，神经重塑进程明显加快。结论：麻黄碱和麻黄碱+纳洛酮各治疗组均能加速脑缺血损伤后大鼠运动功能的恢复速度，促进与神经重塑密切相关的BDNF表达，抑制缺血区神经细胞的凋亡;且随着纳洛酮添加剂量的增加，其作用更加明显，其机制可能与该剂量的纳洛酮能在脑缺血早期显著抑制缺血区神经细胞的凋亡，而与麻黄碱的正性作用形成协同作用而加速神经重塑有关。
Abstract:Objective： To investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity in rats after cerebral ischemia/reperfusion injury to explore the possibility of synergistic effect about ephedrine combined with naloxone， promoting the optimum ratio of neural remodeling and its molecular mechanism. Method： A total of 192 healthy adult Sprague-Dawley rats，220-250 g， were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. Were randomly divided into 8 groups： the rats were intraperitoneally injected with 1.5 mg·kg-1·d-1 ephedrine (ephedrine group)， with 0.1， 0.2， 0.3 mg·kg-1·d-1naloxone (low， moderate and high doses of naloxone groups)， with 1.5 mg·kg-1·d-1 ephedrine + 0.1， 0.2， 0.3 mg·kg-1·d-1 naloxone (ephedrine + low， moderate and high doses of naloxone groups)， and with 0.5 mL saline (model group)， respectively. At 1-4 weeks following cerebral ischemia， sensorimotor integration in rats was assessed using the beam walking test， brain-derived neurotrophic factor (BDNF) expression was detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery. immunofluorescence method of detecting ischemic hemisphere hippocampal expression， The number of nerve cells apoptosis was detected using TUNEL assay. Result： BWT， BDNF， TUNEL assay results showed three doses of naloxone group had no significant effect， the effects increased together with the quantitative ephedrine， and had the amount-effect relationship， in which ephedrine + high dose of naloxone group the recovery of movement was fastest， BDNF expression in the best and ischemic apoptosis in the hippocampus at least， ischemic injury to the minimum， speed up the process of neural remodeling.Conclusion： The ephedrine and ephedrine + naloxone groups were accelerated motor function recovery rate in rat after cerebral ischemia， and the promotion of neural remodeling is closely related to the expression of BDNF， inhibit apoptosis in ischemic area， and with the increase of naloxone amount of additives， its role more clearly， the mechanism may be related to the dose of naloxone can significantly inhibit the ischemic area of apoptosis in early cerebral ischemia， so had the positive synergy effect with ephedrine to speed up the formation of neural remodeling.