椎间孔注射多柔比星对神经病理性痛大鼠痛行为学及背根神经节神经元超微结构的影响  

Effects. of paravertebral injection of doxorubicin on pain behavior and ultrastructure of dorsal root ganglion neurons in rats with neuropathic pain

作　　者：刘靖芷[1] 薄存菊[1] 李全波[1] 史可梅[1] 马文庭[1] 郑宝森[1] 

机构地区：[1]天津医科大学第二医院疼痛治疗中心,300211

出　　处：《中华麻醉学杂志》2012年第6期665-669,共5页Chinese Journal of Anesthesiology

基　　金：天津市自然科学基金（09JCYBJCl3200）

摘　　要：目的评价椎间孔注射多柔比星对神经病理性痛大鼠痛行为学和背根神经节（DRG）神经元超微结构的影响。方法健康雄性SD大鼠100只，体重200～250g，3月龄，采用坐骨神经分支选择性损伤（SNI）的方法建立大鼠神经病理性痛模型，采用随机数字表法，将大鼠随机分为5组（n=20）：SNI组和不同浓度多柔比星组（A1组、A2组、气组和A4组），于模型建立2周后，L4-5和L5-6椎间孔分别注射生理盐水、0．25％、0．50％、0．75％和1．00％多柔比星5μl。于给药前及给药后1～28d测定热辐射缩足潜伏期及冷刺激缩足持续时间，于给药后28d取3只大鼠，取DRG，电镜下观察大、小神经元超微结构。结果与SNI组比较，A1组、A2组、A3组及A4组热辐射缩足潜伏期延长，冷刺激缩足持续时间缩短，呈浓度依赖性（P〈0．05）。电镜下SNI组DRG神经元超微结构未见异常，A1组、A2组、A1组和凡组DRG小神经元细胞核固缩、线粒体肿胀、溶酶体增多、染色质边集、细胞间质纤维化和细胞坏死，而大神经元线粒体肿胀及纤维增多，多数大神经元存活。结论椎间孔注射多柔比星可减轻大鼠神经病理性痛，可导致DRG大、小神经元损伤，小神经元的损伤更明显。Objective To investigate the effects of paravertebral injection of doxorubicin on pain behavior and ultrastructure of dorsal root ganglion （DRG） neurons in rats with neuropathic pain. Methods One hundred male SD rats, aged 3 months, weighing 200-250 g, were studied. The spared nerve injury （SNI） model was estab- lished by ligation and separation of tibial and common fibular nerves. The rats were randomly divided into 5 groups （ n = 20 each） ： SNI group and different concentrations of doxorubicin groups （groups AI , A2, A3, A4 ） ; The animals were anesthetized with intraperitaneal 10 % chloral hydrate 0.3 ml/100 g. The L4-6 intervertebral foramina was exposed. Normal saline and 0.25% , 0.50% ; 0.75% and 1.00% doxorubicin 5 μl were injected into the intervertebral foramina in groups SNI, A1 , A2 , A3 , and A4 respectively. The paw withdrawal latency to the radiant heat stimulation （PWL） and paw withdrawal duration to acetone （PWD） were measured before administration and on day 1-28 after administration. Three rats were chosen in each group on day 28 after administration and DRG were removed to observe the uhrastructure of large and small neurons with electron microscope. Results Compared with group SN1, PWL was significantly prolonged and PWD was significantly shortened in groups A1 , A2, A3, A4 in a concentration manner （ P 〈 0.05）. Nucleus condensation, mitochondrial swelling, increased lysosomes, chromatin condensation, fibrosis of intercellular substances, and cell necrosis were observed in small neurons. Mitochondrial swelling and increased fibers were observed in large neurons and most of large neurons survived. Conclu- sion Paravertebral injection of doxorubicin can reduce neuropathic pain and result in damage to large and small DRG neurons, and small neurons in the DRG are more susceptible and vulnerable to doxorubicin than large neurons in rats.

关 键 词：多柔比星 注射 脊髓 神经节 脊 神经痛 神经元 

分 类 号：R965[医药卫生—药理学]