拉莫三嗪及L-硝基精氨酸对颞叶癫痫一氧化氮合酶活性、一氧化氮含量及nNOS阳性神经元形态结构的影响

doi:10.11843/j.issn.0366-6964.2015.01.018

畜牧兽医学报 ›› 2015, Vol. 46 ›› Issue (1): 138-143.doi: 10.11843/j.issn.0366-6964.2015.01.018

拉莫三嗪及L-硝基精氨酸对颞叶癫痫一氧化氮合酶活性、一氧化氮含量及nNOS阳性神经元形态结构的影响

李猛猛，尹逊河^*，邱建华，王宪龙，李囡

（山东农业大学动物科技学院，泰安 271018）

收稿日期:2014-05-23 出版日期:2015-01-23 发布日期:2015-01-23
通讯作者: 尹逊河（1955-），教授，E-mail：xhyin@sdau.edu.cn，xhyin@163.com
作者简介:李猛猛(1988-)，女，山东淄博人，硕士，主要从事神经解剖与神经生物学研究，E-mail：limengmengshannong@126.com
基金资助:
国家自然科学基金项目（30671498）；山东省自然科学基金项目（Y2003D04）

The Influence of Lamotrigine and L-NNA on the Content of Nitric Oxide and the Activity Nitric Oxide Synthase and nNOS Positive Neurons Morphology in the Temporal Lobe Epilepsy Rabbit Induced by Pilocarpine

LI Meng-meng,YIN Xun-he^*，QIU Jian-hua，WANG Xian-long，LI Nan

(College of Animal Science and Technology，Shandong Agricultural University，Tai’an 271018，China)

Received:2014-05-23 Online:2015-01-23 Published:2015-01-23

摘要/Abstract

摘要：

通过测得家兔颞叶癫痫模型中一氧化氮合酶（NOS）的活性和一氧化氮（NO）的含量，研究L-NNA和拉莫三嗪对其含量变化的影响，探讨NO在颞叶癫痫中的发作机制及这两种药物对脑部神经元的保护作用。选取2.0~2.5 kg健康哈白兔60只，随机分为正常对照组、癫痫模型组、拉莫三嗪治疗组和L-NNA治疗组，应用硝酸还原法测定癫痫发作后不同时间脑组织中海马及颞叶NO的含量及NOS的活性。结果显示：发现模型组脑海马及颞叶内NOS 的活性从6 h开始迅速升高，1 d达到峰值，随后逐渐降低，7 d后基本恢复正常水平，但仍高于其他各组（P<0.05）。L-NNA治疗组和拉莫三嗪治疗组在各时间点极显著或显著低于模型组（P<0.01或P<0.05），L-NNA在6 h~1 d时对NOS的降低程度显著好于拉莫三嗪组（P<0.05）。NO的变化规律与NOS变化规律基本一致且成正相关；利用SABC免疫组化染色检测脑海马内神经性NOS（nNOS）阳性神经元，发现模型组海马内CA3区nNOS阳性神经元密度增加，胞质着色加深，胞体的截面积和突起变小；拉莫三嗪治疗组和L-NNA治疗组的神经元密度有所降低，胞体的截面积和突起长度显著变大（P<0.05）。结果显示：NO参与了颞叶癫痫发作的始动过程，高浓度的NO对神经元有损伤作用；L-NNA和新型治疗药拉莫三嗪能明显抑制癫痫发作后NO的浓度，对脑部神经元有一定的保护作用，从而对癫痫发作有较好的治疗作用。

Abstract:

By measuring the content of Nitric Oxide and the Activity of Nitric Oxide synthase， this experiment was conducted to study the influence of lamotrigine and L-NNA on the change and investigate the mechanism of the action of NO on the cerebral hemorrhageand the protective effect of those two pharmaceuticals in the temporal lobe epilepsy rabbit induced by pilocarpine.Sixty healthy Haerbin rabbits，2.0-2.5 kg，were divided into the group of physiological saline，the epilepsy model group，and the treatment group of lamotrigine and L-NNA.Nitric Oxide （NO） content and the activity of NOS in the hippocampus and temporal lobe after epilepsy were determined by using nitrate enzyme reduction method.We found that the activity of NOS increased at 6 hours after epilpsy， and increased to the highest at 1 day， then decreased gradually and basically returned to normal level after 7 days，but it was still higher significantly than that of other groups （P<0.05）.The level of NOS in two therapy groups between L-NNA and lamotrigine were lower than that in model group at every time extremely notable difference or notable difference （P<0.01 or P<0.05），and the decreasing level of NOS in L-NNA group was lower than that of group of lamotrigine between 6 h to 1 day （P<0.05）.The change of the NO content and the activity of NOS were accordant primitively and directly correlation.SABC immunohistochemical method was used to detect the neuronal NOS positive neurons in hippocampus，the density of neuronal NOS positive neurons in hippocampus’ CA3 region increased，and the cytoplasm stained darker， soma-sectional area and the length of tuber became smaller; After the treatment of lamotrigine and L-NNA，the density of neuron decreased，and the soma-sectional area and the length of tuber became significant longer （P<0.05）.The results indicate that NO is involved in the initiating process of the temporal lobe seizures，and the high concentration of NO can damage the neurons；L-NNA and the novel therapeutic drug lamotrigine can inhibit the concentration of NO after epilepsy seizures，which have a better therapeutic effect on the epilepsy seizures.

中图分类号:

R742.1

李猛猛，尹逊河，邱建华，王宪龙，李囡. 拉莫三嗪及L-硝基精氨酸对颞叶癫痫一氧化氮合酶活性、一氧化氮含量及nNOS阳性神经元形态结构的影响[J]. 畜牧兽医学报, 2015, 46(1): 138-143.

LI Meng-meng,YIN Xun-he，QIU Jian-hua，WANG Xian-long，LI Nan. The Influence of Lamotrigine and L-NNA on the Content of Nitric Oxide and the Activity Nitric Oxide Synthase and nNOS Positive Neurons Morphology in the Temporal Lobe Epilepsy Rabbit Induced by Pilocarpine[J]. ACTA VETERINARIA ET ZOOTECHNICA SINICA, 2015, 46(1): 138-143.

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参考文献

［1］吴逊，沈鼎烈.难治性癫痫［J］.中华神经科杂志，1998，31（1）：4.
WU X,SHEN D L.Intractable status epilepticus［J］.Chinese Journal of Neurology,1998,31(1):4.（in Chinese）
［2］王崇甫，尹逊河，邱建华，等.血塞通及L-硝基精氨酸对脑纹状体出血家兔一氧化氮合酶活性、一氧化氮含量的影响［J］.畜牧兽医学报，2012，43（12）：1957-1962.
WANG C F,YIN X H, QIU J H, et al.The influence of xuesaitong and L-NNA on the activity of nitric oxideynthase and the content of nitric oxide in the striatal hemorrhage rabbits［J］.Acta Veterinaria et Zootechnica Sinica, 2012,43(12):1957-1962.（in Chinese）
［3］赵秀鹤，迟兆富，邓小梅，等.癫痫发作后脑内一氧化氮、一氧化氮合酶及相应氨基酸的变化［J］．中国神经精神疾病杂志，2000，26（2）:101-102.
ZHAO X H, CHI Z F, DENG X M, et al. The changes of nitric oxide, nitric oxide synthase and the corresponding amino acid after seizure in brain［J］.Chinese Journal of Nervous and Mental Diseases, 2000,26(2):101-102.（in Chinese）
［4］王琼.拉莫三嗪和乙琥胺对匹罗卡品诱导的颞叶癫痫的神经可塑性影响的研究［D］.太原：山西医科大学，2012.
WANG Q. Neuroplasticity of lamotrigine and ethosuximide on temporal-lobe epilepsy induced by pilocarpine［D］. Taiyuan: Shanxi Medical University, 2012.（in Chinese）
［5］RACINE R J.Modification of seizure activity by electrical stimulation:ⅡMotor seizure［J］.Electroencephalogr Clin Neurophysiol,1972，32(3)：281-294.
［6］张映琦，廖维宏，曾琳，等.匹罗卡品致痫大鼠海马一氧化氮水平和caspase-3 mRNA表达的动态变化［J］．临床神经病学杂志，2005，18（4）：282-284.
ZHANG Y Q, LIAO W H, ZENG L, et al. Dynamic changes of nitrc oxide content and caspase-3 mRNA expression in hippocampus in epileptic rats induced by pilocarpine［J］.Journal of Clinical Neurology,2005,18(4):282-284.（in Chinese）
［7］姚君茹，潘三强，吕来清，等.癫痫大鼠海马结构谷氨酸和nNOS神经元的动态变化［J］.解剖学杂志，2004，27（5）:505-508，488.
YAO J R, PAN S Q, LÜ L Q, et al. The dynamic changes in hippocampal formation of glutamate and nNOS neurons in epileptic rats［J］.Chinese Journal of Anatomy,2004, 27(5):505-508，488.（in Chinese）
［8］施溯筠，张善玉.不同给药途径及剂量的LNNA对小鼠血清一氧化氮及一氧化氮合酶水平的影响［J］．延边大学医学学报，2009，32（2）：96-98.
SHI S Y, ZHANG S Y. Effects of L-NNA with different ways on NOS activity and NO contents in serum of mice［J］.Journal of Medical Science Yanbian University,2009, 32(2): 96-98.（in Chinese）
［9］MARLETTA M A.Nitric oxide synthase：aspects concerning structure and catalysis［J］.Cell，1994，78(6)：927-930.
［10］MILATOVIC D,GUPTA R C,DETTBARN W D.Involvement of nitric oxide in kainic acid-induced excitotoxicity in rat brain ［J］.Brain Res, 2002，957(2):330-337.
［11］阿依努尔•铁，阿提卡•吾布力哈斯木，刘绍明.一氧化氮与癫痫的研究概况［J］.新疆医学，2006，36（6）:149-151.
TIE A，WUBULIHASIMU A，LIU S M. The isolation of NO and epilepsy［J］.Xinjiang Medical Journal,2006, 36(6): 149-151.（in Chinese）
［12］王淑秋，邸伟华，马小茹，等.戊四氮（PTZ）致痫大鼠脑组织NO和NOS变化及灵芝孢子粉干预［J］.黑龙江医药科学，2011，34（4）:79-80.
WANG S Q, DI W H, MA X R, et al. The change of NO/NOS and intervention of fungus spores in rats induced by PTZ［J］.Heilongjiang Pharmaceutical Science,2011, 34(4): 79-80.（in Chinese）
［13］DEGIORGIO C M，TOMIYASU U，GOTT P S，et al.Hippocampal pyramidal cell loss in human status epilepticus［J］.Epilepsia，1992，33(1):23-27.
［14］HINTERKEUSER S，SCHRDER W，HAGR G，et al．Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances ［J］．Eur J N Eurosci，2000，12(6)：2087-2096.
［15］王本国，韦朝霞，易咏红，等．匹罗卡品癫痫模型中突触素I的表达及苔藓纤维出芽的动态变化［J］．中华神经医学杂志，2006，5（7）：672-675.
WANG B G, WEI Z X, YI Y H, et al. Expression changes of synapsin I immunoreactivity in hippocampus and dentate gyrus and progression of mossy fiber sprouting in dentate gyrus in pilocarpine—induced epilepsy model［J］.Chinese Journal of Neuromedicine,2006,5(7): 672-675.（in Chinese）
［16］李国良，张宁，李静，等.匹罗卡品诱导颞叶癫痫大鼠齿状回苔藓纤维出芽及突触重建［J］.中南大学学报(医学版)，2004，29（4）:424-428.
LI G L, ZHANG N, LI J, et al. Mossy fiber sprouting and synapse formation in the dentate gyrus of temporal lobe epilepsy rats induced by pilocarpine［J］.Journal of Central South University (Medical Sciences),2004, 29(4): 424-428.（in Chinese）
［17］TOMAS R B，GREGORY L H．临床癫痫手册［M］.第3版.刘献增，王晓飞，译．北京：人民卫生出版社，2006：203-251.
TOMAS R B，GREGORY L H.Handbook of Epilepsy［M］.LIU X Z,WANG X F,Translate.Beijing:People’s Medical Publishing House,2006:203-251.（in Chinese）

拉莫三嗪及L-硝基精氨酸对颞叶癫痫一氧化氮合酶活性、一氧化氮含量及nNOS阳性神经元形态结构的影响

The Influence of Lamotrigine and L-NNA on the Content of Nitric Oxide and the Activity Nitric Oxide Synthase and nNOS Positive Neurons Morphology in the Temporal Lobe Epilepsy Rabbit Induced by Pilocarpine

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