活性氧参与神经病理性疼痛大鼠脊髓背角神经元凋亡信号转导过程  

Involvement of reactive oxygen species in apoptotic process of neurons in spinal dorsal horn of neuropathic rats

作　　者：葛彦虎[1] 黄美英 陶坤明[1] 刘艳涛[1] 杨立群[1] 俞卫锋[1] 

机构地区：[1]第二军医大学附属东方肝胆外科医院麻醉科,上海200438 [2]浙江省宁海县力洋中心卫生院

出　　处：《上海医学》2010年第8期716-719,I0001,共5页Shanghai Medical Journal

摘　　要：目的观察神经病理性疼痛大鼠模型鞘内注射自由基清除剂后脊髓背角神经元细胞自由基水平和凋亡情况的变化。方法 20只成年雄性Sprague-Dawley大鼠随机分为苯亚甲基叔丁基氮氧化物(PBN)处理组和0.9%氯化钠溶液(NS)对照组,大鼠进行鞘内置管和脊神经结扎,术后每隔24h分别注射PBN和0.9%氯化钠溶液。另选5只大鼠作脊神经结扎的假手术,不进行鞘内置管,不给药。所有大鼠每天测量机械性痛阈,至术后第12天结束。结果 NS对照组大鼠脊神经结扎后机械性痛阈迅速下降,PBN处理组大鼠脊神经结扎后机械性痛阈下降缓慢,整个测定期间PBN处理组的机械性痛阈均显著高于NS对照组(P值均<0.01)。假手术组大鼠的L4～L5脊髓背角细胞内8-羟基-鸟嘌呤(8-OH-G)的水平较低;NS对照组大鼠的L4～L5脊髓患侧背角细胞内8-OH-G的水平明显升高;PBN处理组大鼠的L4～L5脊髓患侧背角细胞内8-OH-G水平升高,但显著低于NS对照组(P<0.05)。假手术组大鼠的L4～L5脊髓背角细胞内浓染的Hoechest的水平低;NS对照组大鼠的L4～L5脊髓患侧背角细胞内浓染的Hoechest的水平明显升高;PBN处理组大鼠的L4～L5脊髓患侧背角细胞内浓染的Hoechest的水平升高,但显著低于NS处理组(P<0.05)。结论脊神经结扎后脊髓背角神经元细胞内活性氧(ROS)水平增加,凋亡的神经元数目增多,用PBN鞘内注射可以减少神经元凋亡的数量,并缓解神经病理性疼痛。ROS促进脊髓背角神经元凋亡的过程,介导了神经病理性疼痛。Objective To observe the changes of free radical levels in spinal neurons and neuron apoptosis of neuropatic rats after spinal nerve ligation,or spinal nerve ligation followed by elimination of reactive oxygen species（ROS）using penyl N-tert-butylnitrone（PBN）.Methods Twenty male adult Sprague-Dawley rats were randomly divided into two groups（PBN group and control group）;subarachnoid catheterization and spinal nerve ligation were performed.Another 5 rats receiving only sham operation served as sham group.Rats in the PBN group and control group received PBN and normal saline once a day for 12 days,respectively.The mechanical thresholds were determined in all rats once a day.Results After spinal nerve ligation,the mechanical thresholds of rats decreased immediately in control group and slowly in the BPN group,and that in the PBN group was significantly higher than that in the NS group（P〈0.01）.The level of 8-OH-G in the dorsal horn of L4-L5 was low in the sham operation group,and the level was greatly elevated in the NS group;the level in the PBN group was also elevated,but was significantly lower than that in the NS group（P〈0.05）.The staining intensity of Heochest was low in the dorsal horn of L4-L5 in the sham operation group,and that in the NS group was greatly elevated;the level in the PBN group was also increased,but was still significantly lower than that in the NS group（P〈0.05）.Conclusion ROS increases in the dorsal neurons after nerve ligation and the number of apoptotic neurons is also increased.Intrathecal injection of PBN can decease neuron apoptosis and relieve neuronpathic pain.ROS promotes the apoptosis of neurons in the dorsal horn of the spinal cord,mediating the neuropathic pain.（Shanghai Med J.2010,33：716-719）

关 键 词：活性氧 凋亡 神经元 苯亚甲基叔丁基氮氧化物 神经病理性疼痛 

分 类 号：R741.02[医药卫生—神经病学与精神病学]