摘要目的 探讨新生期反复惊厥后大鼠的远期神经行为改变及褪黑素(Melatonin)的预防作用.方法 生后6 d(用P6表示,下同)的健康Sprague-Dawley (SD)大鼠24只,采用随机数字法分成4组,每组6只:对照组(CONT)、褪黑素空白对照组(MEL)、惊厥组(Recurrent Seizures,RS)及褪黑素组(RS+ MEL).通过三氟乙醚反复吸入建立新生期大鼠反复惊厥动物模型:RS组每日吸入三氟乙醚诱导惊厥发作5次,每次间隔30 min,连续9 d；RS+ MEL组于惊厥前1 h(上午8:00)腹腔注射褪黑素(55 mg/kg),同样方法吸入三氟乙醚诱导惊厥发作,方法同RS组；MEL组,与RS+ MEL组同样操作但不吸入三氟乙醚.于P24进行神经行为学评分(平面翻正实验、悬崖回避实验、前肢悬吊实验、负向趋地应实验),于P35天进行旷场行为实验.结果 (1)平面翻正实验显示:RS组平面翻正时间[(0.33 ±0.51)s]较CONT组[(1.17±0.40)s]和RS+ MEL组[(0.50±0.54)s]明显缩短,差异有统计学意义(P＜0.05).(2)悬崖回避实验显示:RS组悬崖回避时间[(16.00±6.32)s]较CONT组[(4.00±2.60)s]和RS+ MEL组[(7.67±3.26)s]明显延长(P＜0.05)；(3)前肢悬吊实验显示:RS组前肢悬吊持续时间[(11.67±7.58)s]较CONT组[(49.50±28.96)s]和RS+ MEL组[(24.83±6.61)s]明显缩短(P＜0.05).(4)负向趋地反应实验显示:RS组负向趋地反应时间[(7.67±1.36)s]较CONT组[(4.50±2.66)s]和RS+ MEL组[(6.17±0.75)s]明显延长(P＜0.05).(5)旷场实验显示:RS组延迟时间[(8.17±3.86)s]较CONT组[(3.00±1.41)s]明显延长(P＜0.05).结论 三氟乙醚诱导的新生期大鼠反复惊厥发作会导致神经行为损伤,惊厥发作前应用褪黑素进行预防,能改善惊厥所致神经行为损伤.

abstractsObjective To explore neurobehavioral changes in rats with recurrent seizures and the prevention effect of melatonin.Methods 6-day-old (P6) SD rats were randomly divided into four groups of 24 (n =6):the control group (CONT),melatonin per se group (MEL),recurrent neonatal seizure group (RS) and melatonin administration prior to RS group (RS + MEL).Rats in RS group were subjected to 5 seizures with flurothyl during the first 14 days of life.In RS + MEL group,melatonin was injected at 8:00 before seizures were induced.Neurobehavioral tests including Plane righting experiment,Cliff avoidance test,the grip-strength test and negative geotaxis test were implemented on P24,while open field test on P35.Results (1) Plane righting experiment:the time of plane righting in RS group ((0.33 ± 0.51)s) was significantly shorter than that in the CONT group ((1.17 ± 0.40) s) and RS + MEL group ((0.50 ± 0.54) s) (P ＜ 0.05).(2) Cliff avoidance test:the time of cliff avoidance in RS group ((16.00 ± 6.32) s) was significantly longer than that in CONT group ((4.00 ± 2.60) s)(P ＜ 0.01),while the time of cliff avoidance in RS + MEL group ((7.67 ± 3.26) s) was shorter than that in the RS group (P ＜ 0.05).(3) The grip-strength test:compared with CONT group ((49.50 ± 28.96) s),the time needed to hold on wire in RS group((11.67 ± 7.58)s)was significantly shorter (P ＜ 0.05) and longer in RS+ MEL group ((24.83 ± 6.61) s) (P ＜ 0.05).(4) Negative geotaxis test:the time for rats to turn 180° upward in RS group((7.67 ± 1.36) s) was longer than that in the CONT group ((4.50 ± 2.66) s) and RS + MEL group ((6.17 ± 0.75) s) (P ＜ 0.05).(5) Open field test:the time for rats to begin to run in the RS group ((8.17 ± 3.86) s) was longer than that in the CONT group ((3.00 ± 1.41) s) (P ＜ 0.05).Conclusion The neurobehaviors are damaged following flurothyl-induced recurrent neonatal seizures,and melatonin can reduce the neurobehavioral injury.