目的 探讨布美他尼通过Nogo-A/RhoA调控脑梗死大鼠的轴突再生。方法 颅内注射内皮素（ET-1）制作脑梗死模型。成年雄性大鼠随机分为3组：假手术组、模型组、布美他尼0.2 mg/kg组，每组10只，应用微量注药系统于侧脑室内给药3周，每天1次。每组取5只大鼠用于测量梗死体积，免疫荧光染色检测脑梗死大鼠BDA阳性纤维通过脊髓灰质联合越过中线的长度；采用Western blotting检测synaptophysin和PSD-95水平、和轴突生长抑制因子Nogo-A和RhoA的水平。结果 与模型组比较，布美他尼组BDA阳性纤维通过脊髓灰质联合越过中线的轴突芽生的长度明显增多（P<0.05）。与模型组比较，布美他尼组的synaptophysin和PSD-95水平明显升高（P<0.05）。与模型组比较，布美他尼组Nogo-A和RhoA水平均显著降低（P<0.05）。结论 布美他尼通过Nogo-A/NgR调控脑梗死大鼠的轴突再生，为更好地了解布美他尼发挥作用的可能机制和脑梗死的临床康复提供新的理论基础和治疗靶点。

Objective To discuss the regulation of bumetanide against axonal regeneration in rats with cerebral infarction via Nogo-A/RhoA. Methods Cerebral infarction model was made by intracranial injection of endothelin-1 (ET-1). Adult rats were divided into sham group, model group, and bumetanide 0.2 mg/kg group, and each group had 10 rats. Microinjection system was applied to lateral intraventricular administration. Rats were given drugs for 3 weeks, once daily. The infarct volume was measured in 5 rats in each group. The axon sprout length of BDA positive fiber across union of spinal gray matter into the midline in rats with cerebral infarction was detected by immunofluorescent staining. Synaptophysin, PSD-95, Nogo-A, and RhoA levels was detected by Western blotting. Results Compared with the model group, the axon sprout length of BDA positive fiber across union of spinal gray matter into the midline in the bumetanide group were significantly increased (P<0.05). Compared with the model group, synaptophysin and PSD-95 levels in the bumetanide group were significantly increased (P<0.05). Compared with the model group, Nogo-A and RhoA levels in the bumetanide group was significantly decreased (P<0.05). Conclusion Bumetanide can regulate axonal regeneration in rats with cerebral infarction via Nogo-A/RhoA, providing new theoretical basis and therapeutic targets for better understanding the possible mechanisms and clinical rehabilitation of cerebral infarction.

R966

辽宁省自然科学基金资助项目（20180550530）