Let-7c-1对戊四氮致痫大鼠学习记忆功能的作用

The effects of let-7c-1 on the learning and memory of epileptic rats induced by PTZ

目的研究let-7c-1对戊四氮(pentylenetetrazol,PTZ)致痫大鼠学习记忆功能的影响,探讨其可能机制。方法通过PTZ腹腔注射SD雄性大鼠建立慢性癫痫模型,随机分为癫痫组、干预对照组、let-7c-1激动剂组,各组12只,另设12只大鼠为正常组。28 d后,观察各组大鼠的行为学变化,let-7c-1基因表达及大鼠海马组织中Bcl-2、Caspase3蛋白的表达。结果与正常组相比,癫痫组大鼠逃避潜伏期延长、穿越平台次数减少、在目标象限的总路程缩短,差异有统计学意义(P<0.05);癫痫组与干预对照组相比,逃避潜伏期、穿越平台次数、在目标象限的总路程无统计学差异(P>0.05);与干预对照组相比,let-7c-1激动剂组逃避潜伏期明显延长,穿越平台次数减少、在目标象限的总路程缩短,差异有统计学意义(P<0.05)。干预对照组与let-7c-1激动剂组let-7c-1基因相对表达量分别为(1.35±0.32)、(62.53±21.01)(F=50.97,P<0.05)。癫痫组let-7c-1基因表达量高于正常组,差异有统计学意义(P<0.05)。let-7c-1激动剂组let-7c-1基因表达量明显高于干预对照组、癫痫组及正常组,差异有统计学意义(P<0.05)。与正常组相比,癫痫组的Bcl-2蛋白表达减少,Caspase3蛋白表达增加,差异有统计学意义(P<0.05);癫痫组与干预对照组相比,Bcl-2蛋白及Caspase3蛋白的表达无统计学差异(P>0.05)。与干预对照组相比,let-7c-1激动剂组Bcl-2蛋白表达明显减少,Caspase3蛋白表达明显增加,差异有统计学意义(P<0.05)。结论 Let-7c-1可能通过减少海马组织Bcl-2蛋白及增加Caspase-3蛋白表达使PTZ致痫大鼠的学习记忆功能受损。

Objective To explore the effect of let-7c-1 on the learning and memory of PTZ-induced epileptic rats and its relevant mechanism. Methods A model of temporal lobe epilepsy （TLE） was induced via PTZ kindling in SD male rats. The epileptic rats were divided into epilepsy group, agomir-control group, iet-7c-1 agomir group （12 rats for each）. Twelve rats were served as a negative control group. The behavior and the expression levesl of let-7c- 1, Bcl-2 protein and Caspase3 were evaluated at 28 clays following PTZ. Results Compared to the negative group, the escape latency of epilepsy group was prolonged and the crossing times as well as the quadrant total distance in the target were reduced （P〈0.05）. However, those parameters were not significantly different between the epilepsy group and the agmoir-control group （P〉0.05）. Compared to the agmoir-control group, the escape latency of let-7c-1 agomir group was prolonged and the crossing times as well as the quadrant total distance in the target were reduced （P〈 0.05）. The expression levels of let-7c-1 and let-Tc-1 were 1.35±0.32 in agmoir-control group and 62.53±21.01 in agomir group （F=50.97,P〈0.05）. The expression levels of let-7c-1 were higher in let-7e-1 agomir group than in other groups （P〈0.05）. Compared to the negative group, the expressions of Bcl-2 protein in other groups were de- creased （P〈0.05） and the Caspase3 protein were increased （P〈0.05）. Compared to the agomir-eontrol group, the ex- pression of Bcl-2 protein was significantly decreased and the expression of Caspase3 protein was significantly increased in let-7c-1 agomir group （P〈0.05）. Conclusions The present study shows that let-7c-1 may impair the learning and memory of PTZ-induced epileptic rats through decreasing the Bcl-2 protein and increasing Caspase3 protein in the hippocampus.