褪黑素对大鼠前额叶皮层缺血诱发认知功能障碍的影响及其受体机制

Effect of melatonin on prefrontal cortex ischemia-induced cognitive impairment in rats and the receptor mechanism

目的评价褪黑素对大鼠前额叶皮层缺血诱发认知功能障碍的影响并探讨其受体机制。方法选择清洁级成年雄性SD大鼠,体重约300 g,进行前额叶皮层置管。实验Ⅰ取置管成功的大鼠24只,采用随机数字表法分为3组(n=8):对照组(C组)前额叶皮层注射生理盐水0.5μl;模型组(M组)前额叶皮层微注射1μmol/L内皮素0.5μl;褪黑素组(ME组)前额叶皮层注射1μmol/L内皮素+1μmol/L褪黑素,共0.5μl。实验Ⅱ取置管成功的大鼠44只,采用随机数字表法分为4组(n=11):模型组(M组)前额叶皮层微注射1μmol/L内皮素0.5μl;褪黑素组(ME组)前额叶皮层注射1μmol/L内皮素+1μmol/L褪黑素,共0.5μl;褪黑素1/2型受体(MT_(1/2)R)拮抗剂+褪黑素组(L+ME组)前额叶皮层注射1μmol/L内皮素+1μmol/L MT_(1/2)R拮抗剂和1μmol/L褪黑素,共0.5μl;褪黑素2型受体(MT_(2)R)拮抗剂+褪黑素组(P+ME组)前额叶皮层注射1μmol/L内皮素+1μmol/L MT_(2)R拮抗剂和1μmol/L褪黑素,共0.5μl。前额叶皮层给药后1周进行T-迷宫实验和旷场实验。结果实验Ⅰ3组旷场实验运动速度比较差异无统计学意义(P>0.05)。与C组比较,M组和ME组T-迷宫实验选择正确率下降(P<0.05);与M组比较,ME组T-迷宫实验选择正确率升高(P<0.05)。实验Ⅱ4组旷场实验运动速度比较差异无统计学意义(P>0.05)。与M组比较,ME组和P+ME组T-迷宫实验选择正确率升高(P<0.05),L+ME组差异无统计学意义(P>0.05);与ME组比较,L+ME组T-迷宫实验选择正确率下降(P<0.05),P+ME组差异无统计学意义(P>0.05)。结论褪黑素可减轻大鼠前额叶皮层缺血引起认知功能障碍,机制与激活MT_(1)R有关。

Objective To evaluate the effect of melatonin on prefrontal cortex ischemia-induced cognitive impairment in rats and to investigate the receptor mechanism.Methods Clean-grade adult male Sprague-Dawley rats,weighing 300 g,were selected,and a catheter was implanted into the prefrontal cortex.The experiment was performed in two parts.ExperimentⅠTwenty-four rats,in which catheters were successfully inserted into the prefrontal cortex,were assigned into 3 groups(n=8 each)using a random number table method:control group(group C),model group(group M)and melatonin group(group ME).Normal saline 0.5μl was injected into the prefrontal cortex in group C,1μmol/L endothelin 0.5μl was microinjected into the prefrontal cortex in group M,and 1μmol/L endothelin and 1μmol/L melatonin 0.5μl were injected into the prefrontal cortex in group ME.Experiment Ⅱ Forty-four rats,in which catheters were successfully inserted into the prefrontal cortex,were assigned into 4 groups(n=11 each)using a random number table method:model group(group M),melatonin group(group ME),MT1/2R antagonist luzindole+melatonin group(group L+ME)and MT_(2)R antagonist 4p-pdot+melatonin group(group P+ME).In group M,1μmol/l endothelin 0.5μl was microinjected into the prefrontal cortex.In group ME,1μmol/L endothelin+1μmol/L melatonin 0.5μl was injected into the prefrontal cortex.In group L+ME,1μmol/L endothelin+1μmol/L MT_(1/2)R antagonist+1μmol/L melatonin 0.5μl was injected into the prefrontal cortex.In group P+ME,1μmol/L endothelin+1μmol/L MT_(2)R antagonist+1μmol/L melatonin 0.5μl was injected into the prefrontal cortex.T-maze and the open field tests were performed at 1 week after administration.Results Experiment Ⅰ There was no significant difference in the locomotor speed in open field test among C,M and ME groups(P>0.05).The rate of correct selection in T-maze test was significantly lower in M and ME groups than in group C and higher in group ME than in group M(P<0.05).Experiment Ⅱ There was no significant difference in the locomotor speed in open field test among the four groups(P>0.05).Compared with group M,the rate of correct selection in open field test was significantly increased in ME and P+ME groups(P<0.05),and no significant change was found in group L+ME(P>0.05).Compared with group ME,the rate of correct selection in open field test was significantly decreased in group L+ME(P<0.05),and no significant change was found in group P+ME(P>0.05).Conclusion Melatonin can attenuate prefrontal cortex ischemia-induced cognitive impairment in the rats,and the mechanism is related to activation of MT_(1)R.