延髓头端腹外侧部在脑梗死合并心律失常中的作用

Involvement of the rostral ventrolateral medulla in the cerebral infarction complicated with arrhythmias

目的探讨延髓头端腹外侧部在脑梗死合并心律失常中的作用及可能机制。方法 112只Wistar大鼠随机分为3组:对照组(n=16)、假手术组(n=16)和模型组(n=80)。模型组再随机分为造模后30 min、1 h、2 h、4 h和8 h组,每组16只,观察脑梗死后延髓头端腹外侧部神经元活动的变化。另40只大鼠随机分为5组:对照组(n=8)、生理盐水组(10μL,n=8)、L-谷氨酸组(0.5μmol,10μL,n=8)、谷氨酸非选择性NMDA受体拮抗剂MK-801(4 nmol,10μL)加L-谷氨酸组(n=8)和MK-801加模型组(n=8),以观察谷氨酸在脑梗死诱发心律失常中的作用。心电图用生物信号采集系统采集。脑梗死动物模型制作采用大鼠大脑中动脉栓塞(MCAO),给药途径为侧脑室注射,以Fos蛋白作为神经元激活的标志物。结果对照组和假手术组大鼠心电图均无明显异常,模型组大鼠心律失常的发生率为78.75%(63/80),明显高于对照组(P<0.01),且在心律失常发生的相应时间点延髓头端腹外侧部Fos蛋白表达明显增加(P<0.01)。侧脑室注射生理盐水组心电图无明显异常,侧脑室注射L-谷氨酸后心律失常发生率为87.5%(7/8),明显高于生理盐水组(P<0.01),心律失常类型类似于模型组,同时延髓头端腹外侧部Fos蛋白表达明显增高(P<0.05)。MK-801预处理后再造模和MK-801预处理后再侧脑室注射L-谷氨酸组,均无心律失常发生,延髓头端腹外侧部Fos蛋白表达无显著性变化(P>0.05)。结论脑梗死合并心律失常的发生与延髓头端腹外侧部活动增强有关,且此作用由谷氨酸激活NMDA受体介导。

Objective To investigate the association between ischemic stroke-induced arrhythmia and the activity of rostral ventrolateral medulla（RVLM） and the possible mechanism. Methods 112 Wistar rats were randomly divided into the following 3 groups： control group（n =16）, sham-operated group（n =16）, and model group（n =80）. These rats in the third group were further randomly and equally divided into different time groups（ n=16 per group）, 30 minutes,1 hour, 2 hours, 4 hours and 8 hours. The changes of the activity of RVLM neurons in ischemic stroke rats were observed. 40 rats were randomly and equally divided into 5 groups（n=8 per group）： control group, saline（10 μL） group,L-glutamate（0.5 μmol, 10 μL） group, MK-801（4 nmol, 10 μL） before L-glutamate group, and MK-801 preceding making model group. The effects of glutamate on arrhythmia induced by ischemic stroke were observed. The electrocardiography was recorded by a biological signal collecting and processing system. The experimental cerebral ischemic animal model was established by occluding the right middle cerebral artery（MCAO）. Fos protein was used as an objective indicator to illustrate the functional state of neurons in RVLM. Results The incidence of arrhythmia, 78.75%（63/80） in model group was significantly higher than controls（P〈0.01）, and Fos protein expression in the RVLM also increased significantly（P〈0.01）, both of them could be blocked by prior application of MK-801. The incidence of arrhythmia in intracerebroventricular injection of L-glutamate group was 87.5%（7/8）, which was significantly higher than saline group（P〈0.01） and Fos protein expression in the RVLM also increased significantly（P〈0.05）. These changes could be blocked by prior application of MK-801. Conclusion It is concluded that activation of the RVLM in ischemic stroke rats is likely mediated by glutamate via activation of N-methyl-D-aspartic acid（NMDA） receptors, which causes arrhythmias.