莫达非尼对72h快速眼动睡眠剥夺大鼠海马基质金属蛋白酶9和认知功能的影响  

Effects of modafinil on hippocampal matrix metalloproteinase-9 and cognitive function in 72 h rapid-eye-movement sleep deprived rats

作　　者：贺斌[1] 彭华[1] 赵忠新[1] 

机构地区：[1]中国人民解放军第二军医大学附属长征医院神经内科,上海200003

出　　处：《中国新药与临床杂志》2014年第2期146-150,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：上海市科学技术委员会资助课题(05ZR14155;08411950700)

摘　　要：目的研究莫达非尼对72 h快速眼动(REM)睡眠剥夺大鼠海马基质金属蛋白酶9(MMP-9)和认知功能的影响。方法将成年雄性SD大鼠随机分为五组(n=6):正常对照组(CC)、环境对照+空间训练组(TC)、空间训练+REM睡眠剥夺组(SD)、SD+莫达非尼200 mg·kg^(-1)·d^(-1)×3 d组(MD)、SD+安慰剂对照组(CMC)。大鼠的空间训练采用Y型迷宫。用改良多平台睡眠剥夺法建立REM睡眠剥夺模型。应用免疫印迹方法测定MMP-9的蛋白质水平。RT-PCR检测MMP-9 mRNA的相对含量。结果TC组比CC组错误反应次数(EN)显著减少(P<0.05),SD组比TC组EN显著增多(P<0.01),CMC组与SD组无显著差别(P>0.05),MD组比CMC组EN显著减少(P<0.01)。TC组比CC组MMP-9蛋白含量显著增高(P<0.01);经72 h睡眠剥夺后,SD组比TC组MMP-9蛋白含量显著增高(P<0.01),而与CMC组比较无显著差异(P>0.05);给予莫达非尼72 h后,MD组比CMC组MMP-9蛋白含量显著降低(P<0.01)。经RT-PCR检测MMP-9 mRNA表达的结果在上述各组中与免疫印迹检测的结果相一致。结论莫达非尼显著提高72 h REM睡眠剥夺大鼠认知功能,可能与其调节MMP-9 mRNA表达有关。AIM To evaluate the effects of modafinil on the expression of hippocampal matrix metalloproteinase- 9 （MMP-9） and cognitive function in rats with 72 h rapid-eye- movement （REM） sleep deprivation. METHODS Adult male SD rats were randomly assigned into five groups （n = 6）, including home cage controlled （CC） group, platform controlled and Y maze trained （TC） group, Y maze trained and REM sleep deprived （SD） group, REM sleep deprived and modafinil 200 mg-kg-I .d-1 ~ 3 d （MD） group, andREM sleep deprived and placebo controlled （CMC） group. Y maze was applied for learning skill measurement. The modified multiple platform method was used to create the sleep deprived animal model. Western blot and real time PCR were respectively employed to detect the expression of MMP-9 in hippocampus. RESULTS The values of error numbers （ENs） in TC group were significantly decreased compared with those in CC group （P 〈 0.05）, while the ENs in SD group were higher than those in TC group （P 〈 0.01）. The ENs in MD group were less than those in CMC group （P 〈 0.01 ） and there was no significant difference between CMC and SD group （P 〉 0.05）. The hippocampal MMP-9 level in the TC group was higher than that in CC group （P 〈 0.01）. With a 72 h rapid-eye-movement sleep deprivation, MMP-9 expression was significantly increased in SD group than that in TC group （P 〈 0.01）. MMP-9 in CMC group was comparable to that in SD group （P 〉 0.05）. The hippocampal MMP-9 in MD group treated with modafinil 200 mg. kg-i＇d-1 for 3 days was decreased significantly than that in CMC group （P 〈 0.01）. The hippocampal MMP-9 mRNA levels detected by real time PCR were consistent with the MMP- 9 protein level detected by Western blot. CONCLUSION Modafinil significantly improves cognitive function in rats with 72 h REM sleep deprivation, which might be related to the regulation of MMP-9 mRNA expression.

关 键 词：REM深眠状态 睡眠剥夺 莫达非尼 海马 

分 类 号：R961[医药卫生—药理学]