氯胺酮抗惊厥的作用机制  

Study on anticonvulsant mechanism of ketamine

作　　者：孟晶[1] 翟云鹏[2] 段世明[1] 马涛[1] 戴体俊[1] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,江苏徐州221002 [2]徐州医学院药理学教研室,江苏徐州221002

出　　处：《中国药理学通报》2009年第9期1185-1188,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No39970715;30471657;30872432);江苏省高校自然科学基础研究资助项目(No07KJD310219)

摘　　要：目的观察氯胺酮对惊厥小鼠不同脑区Na+,K+-ATP酶、Ca2+-ATP酶以及NOS酶活性的影响,探讨氯胺酮抗惊厥作用的中枢机制。方法昆明种小鼠随机分成空白组、生理盐水(NS)组、氯胺酮25mg·kg-1(KetⅠ)和50mg·kg-1(KetⅡ)组。空白组直接断头取脑。其余各组分别ip相应药物,5min后ip士的宁1.5mg·kg-1诱发惊厥,观察惊厥小鼠行为学变化,并于给士的宁30min后断头,用分光光度计法测定皮层额、顶、枕脑区的Na+,K+-ATP酶、Ca2+-ATP酶和NOS酶活性。结果氯胺酮组明显降低动物死亡率,KetⅡ组惊厥持续期较KetⅠ组明显缩短。与空白组相比,NS组和KetⅠ组Na+,K+-ATP酶、Ca2+-ATP酶活性均有降低,KetⅡ组顶、枕区Na+,K+-ATP和Ca2+-ATP酶活性维持在正常水平;KetⅡ组TNOS酶活性降低约1/3(P<0.05),各组对iNOS活性均无影响。结论氯胺酮抗惊厥作用机制可能与增加大脑皮层顶枕区的Na+,K+-ATP和Ca2+-ATP酶活性、降低cNOS酶活性有关。Aim To observe the effects of ketamine on Na＋, K ＋-ATPase, Ca2＋-ATPase and NOSase activity in different cerebral cortex in convulsive mice. Methods The mice were randomly divided into blank group, normal saline （NS） group and ketamine 25 mg ·kg^-1 （ Ket Ⅰ ）, 50 mg·kg^-1 （ KetⅡ ） group. The animals of blank group were killed directly. Convulsion was induced by intraperitoneally （ip） strychnine （ 1.5 mg ·kg^-1 ） in other groups, and correspond drugs were administered ip before five minutes. Action variety of mice was observed. Animals were killed on 30 minutes after strychnine injection. The activity of Na ＋ , K＋ -AT- Pase, Ca2＋-ATPase, TNOSase and iNOSase were assessed by spestrophotometric analysis in different cerehral cortex（forehead, parietal and occipital area）. Resuits Ketamine group could decrease mortality completely. The duration of tonic state in Ket Ⅲgroup was significantly shorter than that in Ket Ⅰgroup. Compared with blank group, Na ＋ , K ＋-ATPase and Ca2 ＋ -ATP ase activities were decreased in the group of NS and Ket Ⅰ , and recovered normal level in the group of Ket Ⅱat parietal and occipital area. TNOS ase activity was decreased by 1/3 in KetⅡgroup（ P 〈 0.05 ） , and iNOSase activity was not affected in all groups. Conclusion The increase of Na ＋ , K ＋ -ATPase, Ca2＋- ATP ase activity in parietal and occipital area and the decrease of cNOSase activity may be involved in the anticonvulsant mechanism of ketamine.

关 键 词：氯胺酮 抗惊厥 大脑皮层 机制 Na+ K+-ATP酶 CA2+-ATP酶 NOS酶活性 

分 类 号：R-332[医药卫生] R322.81