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出 处:《中国药学杂志》2008年第6期427-430,共4页Chinese Pharmaceutical Journal
基 金:国家重点基础研究发展规划项目(G2000057010)
摘 要:目的研究蕃荔枝酰胺新衍生物cFLZ对小鼠实验性学习记忆功能障碍的影响。方法选用体积分数40%乙醇、戊巴比妥钠(20 mg·kg^(-1))、环己酰亚胺(120 mg-kg^(-1))造成小鼠学习记忆障碍模型,分别通过避暗法、跳台法、水迷津法观察提前口服不同剂量的cFLZ对小鼠学习记忆能力障碍的作用。结果①小鼠口服体积分数为40%乙醇后出现明显记忆障碍,避暗法实验中表现在第一次进入暗室的潜伏期明显缩短(P<0.01),3 min内进入暗室的次数显著增加(P<0.01)。与模型组相比,cFLZ(75,150 mg·kg^(-1))组小鼠第一次进入暗室的潜伏期延长(P<0.05),3 min内进入暗室的次数减少(P<0.05);②水迷津法实验中随着路径的延长和盲端的增多,腹腔注射戊巴比妥钠(20 mg·kg^(-1))模型组小鼠游到目的地的时间比正常对照组明显延长,进入盲端的错误次数也明显增加。与模型组相比,cFLZ(75,150 mg·kg^(-1))组小鼠能够缩短游到目的地的时间(P<0.05),减少进入盲端的错误次数(P<0.05)。③跳台法实验中小鼠腹腔注射环己酰亚胺(120 mg·kg^(-1))后引起显著的记忆巩固障碍,第一次跳下安全岛的时间明显缩短(P<0.01),5 min内跳下的次数显著增加(P<0.01)。cFLZ(37.5,75,150 mg·kg^(-1))可显著改善环己酰亚胺诱导的记忆障碍,延长第一次跳下安全岛的潜伏期(P<0.05),减少跳下的次数(P<0.01)。结论蕃荔枝酰胺新衍生物cFLZ对体积分数40%乙醇、戊巴比妥钠及环己酰亚胺诱导的小鼠学习记忆功能障碍有明显改善作用。OBJECTIVE To study the effects of a novel synthetic squamosamide cyclic analogue (cFLZ) on experimental disturbance of learning and memory function in mice. METHODS Ethanol (40%) , sodium pentobarbital (20 mg·kg^-1 ) and cycloheximide ( 120 mg·kg^-1 ) were used to induce mouse learning and memory disturbance, respectively. The improving effect of oral administration of cFLZ was observed by passive avoid test, water maze test, and step-down test, respectively. RESULTS (1) In passive avoidance test, an oral dose of 40% ethanol (10 mL · kg^-1, ig) induced mouse memory reappearance dysfunction. In compared with the model group, cFLZ (75, 150 mg·kg^-1 ) given orally significantly reduced error times and prolonged the latency time. (2)In water maze test, an intraperiteneal dose of sodium pentobarbital (20 mg·kg^-1, ip) induced spatial dysfunction expressed by the prolongation of swimming time and increase of the number of errors, cFLZ (75, 150 mg·kg^-1 ) shortened the swimming time and decreased the number of errors. (3)In step-down test.cyeloheximide ( 120 mg·kg^-1 , ip) induced memory retention dysfimction in mice. The latency of the first step-down was reduced and the number of electric shock in 5 rain was increased, cFLZ (37.5, 75, 150 mg·kg^-1 ) significantly prulonged the latency of the first step-down and decreased the number of electric shock in 5 min. CONCLUSION cFLZ has remarkable improving effect on experimental disturbance of learning and memory function induced by ethanol, sodium pentobarbital and cycloheximide in mice.
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