KA致癎大鼠海马神经元凋亡和一氧化氮合成酶关系的研究  

A STUDY OF THE RELATIONSHIP BETWEEN HIPPOCAMPUS NEURONAL APOPTOSIS AND NOS EXPRESSION IN RATS AFTER KAINIC ACID-EVOKED SEIZURES

作　　者：吴原[1] 庞家容[1] 郑金瓯[1] 李佳荃[2] 邓晓清[1] 梁秀琳[1] 陈志颖[3] 

机构地区：[1]广西医科大学第一附属医院神经内科,南宁530021 [2]广西医科大学医学科学实验中心 [3]广西医科大学第一附属医院脑电图室

出　　处：《广西医科大学学报》2008年第1期17-20,共4页Journal of Guangxi Medical University

基　　金：广西科技厅回国基金资助项目(No桂科回0342012)

摘　　要：目的:探讨红藻氨酸(kainic acid,KA)诱导的癫癎大鼠海马神经元凋亡和一氧化氮合成酶在不同部位和致癎后不同时间的变化情况。方法:50只SD大鼠随机分为对照组、KA组,KA组再按癫癎发作后1d、1周、2周、3周和4周不同时点分为5个亚组。注射KA后,观察大鼠癫癎发作后的行为学变化,采用原位细胞凋亡检测法观察海马神经元凋亡情况;采用免疫组化的方法观察3种不同一氧化氮合成酶(iNOS、nNOS和eNOS)的表达。结果:KA注射后,大鼠出现严重的惊厥,癫癎发作后1d、1周即有大量的凋亡细胞出现在海马齿状回、CA1,CA2和CA3区,2、3周时下降,第4周出现另一个高峰,凋亡在齿状回和CA3区最明显。癫癎发作后早期即有大量的eNOS,iNOS和nNOS出现,另一方面,nNOS在齿状回表现为低表达,eNOS阳性细胞在齿状回、CA1、CA2区的表达也与凋亡的出现基本同步,而在CA3区却表现为癫癎发作后1d和1周出现少,在2周后才随时间的推移有逐渐增加,结论:凋亡参与KA致大鼠癫癎发作后神经元死亡过程,eNOS,iNOS和nNOS与癫癎发作后早期的神经原凋亡相关,iNOS与齿状回癫癎后迟发的神经原凋亡可能有关;nNOS与CA2和CA3区的癫癎后迟发的神经原凋亡可能有关;eNOS对KA致大鼠癫癎发作后CA3区神经元凋亡可能有神经保护作用。Objective：To study of the relationship between hippocampus neuronal apoptosis and NOS expression in rats after Kainic Acid-evoked seizures. Methods： 50 SD rats were classified as control group, KA group. The KA groups were also divided into 5 sub-groups （1 d,1 W,2 W,3 W and 4 W） according to seizure attack at the different time-point. To observe the change of ethology after seizure attack, the change of neuronal apoptosis with in situ terminal deoxynucleotidyl transferase Dutp nick-end labeling （TUNEL stain）, and immunohistochemistry were used to test the expression of NOS （including iNOS, nNOS and eNOS）. Result： The rats appeared severe seizures after injecting KA; there were more apoptotic positive cells in dentate gyrus, CA1, CA2 and CA3 sectors on ld and 1 W and they decreased in 2 W and 3 W, and there were another peak in 4 W. The numbers of apoptotic positive cells of dentate gyrus and CA3 sectors significantly increased. The expression of iNOS, nNOS and eNOS were in conformity with the change of neuronal apoptosis in earlier period, iNOS would be concerned with tardus neuronal apoptosis of dentate gyrus, nNOS would be concerned with tardus neuronal apoptosis of CA2 and CA3. On the other hand, nNOS was lower in dentate gyrus, so the neuronal apoptosis of dentate gyrus would be concerned with iNOS but not nNOS. eNOS positive cells were conformity with the change of neuronal apoptosis in dentate band, CA1 and CA2 sectors, but the eNOS positive cells of CA3 were fewer than control group in earlier period （1 d and 1 W）. It increased gradually after 2 W. Conclusion： Apoptosis participates in the process of neuronal death in KA-evoked seizures in rats. The expression of iNOS, nNOS and eNOS were conformity with the change of neuronal apoptosis in earlier period, iNOS would be concerned with tardus neuronal apoptosis of dentate gyrus, nNOS would be concerned with tardus neuronal apoptosis of CA2 and CA3. eNOS would be neuroprotective effect in CA3.

关 键 词：癫痫 红藻氨酸 海马 细胞凋亡 一氧化氮合成酶 

分 类 号：R742.1[医药卫生—神经病学与精神病学]