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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Koi-zumi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。
OBJECTIVE: To compare the changes of neuroplasticity induced by ephedrine and naloxone after different doses of naloxone in rats, and to explore whether ephedrine can produce synergetic effect after compatibility with naloxone and promote the optimal of nerve remodeling Proportion and its molecular mechanism. METHODS: A total of 192 SD rats weighing 220-250 g were used to establish the left MCAO model by modified Koi-zumi suture method. The rats were randomly divided into 8 groups: natural rehabilitation group (0.5 mL), ephedrine group (1.5 mg.kg-1.d-1) and low-dose naloxone treatment group (0.1 mg.kg-1.d-1) (0.2 mg.kg-1.d-1), naloxone high-dose group (0.3 mg.kg-1.d-1), ephedrine + low-dose naloxone (1.5 mg.kg-1.d-1), ephedrine + mid-dose naloxone treatment group (1.5 mg.kg-1.d-1), ephedrine + high-dose naloxone treatment group kg-1.d-1), administered 3 times daily, intraperitoneal injection. Postoperative 1, 2, 3, 4 weeks after operation, the walking test was used to evaluate the recovery of sensory and motor function in rats. The expression of BDNF in hippocampus was detected by immunofluorescence method. The apoptosis of neurons number. Results: The crossbark walking test, BDNF and TUNEL staining showed that no significant effect was observed in the three dosage groups of naloxone. After the quantitative ephedrine treatment, the effect was increased and there was a dose-effect relationship. Ephedrine + high-dose naloxone treatment The recovery of motor function was the fastest, the expression of BDNF was the best, and the number of apoptotic neurons in hippocampus was the least. The ischemic injury was the lightest and the process of nerve remodeling was obviously accelerated. Conclusion: Both ephedrine and ephedrine + naloxone treatment groups can accelerate the recovery of motor function after cerebral ischemia injury, promote the expression of BDNF, which is closely related to nerve remodeling, and inhibit the apoptosis of ischemic nerve cells ; And with the increase in the amount of naloxone, its effect is more obvious, the mechanism may be that the dose of naloxone can significantly inhibit the ischemic neuronal apoptosis early in the cerebral ischemia, and ephedrine positive Synergy of sexual roles and acceleration of neural remodeling.