脊髓电刺激对缓激肽诱发的心脏伤害性感受的抑制作用

Inhibitory effect of spinal cord stimulation on cardiac nociception induced by intrapericardial bradykinin injection in rat model

目的：观察脊髓电刺激（SCS）对缓激肽（BK）诱发的心脏伤害性感受的调节作用,并探讨其作用机制。方法：42只雄性健康SD大鼠随机分为电生理实验（N=17）和免疫组织化学实验（N=25）,所有实验动物均实施心包插管术以诱发心脏痛。电生理实验大鼠随机分为BK心脏重复刺激组（n=5）和BK加SCS组（n=12）,以心包内可重复性注入致痛剂BK所诱发的背斜方肌肌电（EMG）变化百分比为观察指标,评估SCS对BK所诱发的EMG的下行调控作用;免疫组织化学实验大鼠随机分为空白对照组（n=3）、生理盐水对照组（n=4）、SCS对照组（n=6）、BK心脏痛模型组（n=6）和BK加SCS组（n=6）,以心包内注射BK所诱发的T3～T5节段脊髓背角c-fos表达水平为伤害性评价指标,评估SCS对BK所诱发的c-fos表达水平的影响。结果：电生理实验,与BK心脏重复刺激组比较,BK加SCS组EMG变化百分率降低（P〈0.05）;SCS结束5min后,EMG为基础对照的54.02%±4.95%（P〈0.05）;SCS结束55min后,EMG为基础对照的74.82%±4.74%（P〈0.05）;SCS结束105min后,EMG恢复至基础对照水平。免疫组织化学实验,生理盐水对照组和SCS对照组大鼠c-fos表达水平分别为22.50±1.85和35.00±3.77,与空白对照组（15.00±2.87）比较差异无统计学意义（P〉0.05）;BK心脏痛模型组大鼠脊髓背角c-fos表达水平（115.67±10.05）明显高于空白对照组（P〈0.05）;BK加SCS组大鼠c-fos表达水平（59.83±5.76）与BK心脏痛模型组比较明显降低（P〈0.05）。结论：SCS对BK诱发的EMG反应和脊髓背角伤害性信号c-fos表达均具有抑制效应,这种抑制效应很可能是由于SCS激活了颈段脊髓抑制性中间神经元,继而这些抑制性神经元通过降低胸段脊髓心脏伤害性感受神经元的活动而抑制了心脏伤害性感受。

Objective To observe the regulation effect of spinal cord stimulation（SCS）on the cardiac nociception of the rats induced by bradykinin（BK）,and to explore its mechanism.Methods 42 male healthy SD rats were randomly divided into electrophysiological experiment part（N=17）and immunohistochemistry part（N=25）.All the rats were implemented cardiac catheterization to evoke heart pain.In electrophysiological experiment part,the rats were divided into BK reproducibility group（n=5）and BK＋SCS group（n=12）,and the electromyogram（EMG）percentage changes of dorsal spinotrapezius muscle evoked by BK were used as study indexes to examine the descending modulation of SCS on the cardiac nociception.In immunohistochemistry part,the rats were divided into control group（n=3）,saline group（n=4）,SCS group（n=6）,BK group（n=6）and BK＋SCS group（n=6）.The expression level of c-fos in T3-T5 spinal dorsal horn was used as nociceptive evaluation to assess the protective effect of SCS on the cardiac nociception.Results Compared with BK reproducibility group,the EMG percentage in BK＋SCS group was decreased（P〈0.05）,and the EMG declined to（54.02±4.95）% of control at 5min after SCS（P〈0.05）;at 55 min after SCS,the EMG recovered to（74.82±4.74）% of control（P〈0.05）and 105 min later,the EMG recovered to control level.Moreover,compared with control group（15.00± 2.87）,the expression levels of c-fos in saline control group（22.50±1.85）and SCS group（35.00±3.77）had no significant differences（P〉0.05）.The expression levels of c-fos in BK group（115.67±10.05）in T3-T5 spinal cord dorsal horn was higher than that in control group（P〈0.05）,and the expression level of c-fos（59.83±5.76）in BK＋SCS group was significantly lower than that in BK group（P〈0.05）.Conclusion SCS can significantly inhibit the EMG and c-fos expression level induced by BK,which may be attributed to that SCS activates the spinal inhibitory interneurons and these inhibitory interneurons suppress the activities of cardiac pain sensitive neurons.