胞二磷胆碱对氯胺酮麻醉致幼期大鼠长期认知功能损害的影响

Effects of citicoline on ketamine-induced longer learning and memory injury in young rats

目的:探讨胞二磷胆碱对氯胺酮麻醉致幼期大鼠长期认知功能损害的治疗作用。方法:54只雄性PND7大鼠幼鼠根据出生时间和处理方式分成9组:114 d对照组(C14d组)、14 d氯胺酮组(K14d组)、14 d异氟烷+胞二磷胆碱组(K+C14d组);230 d对照组(C30d组)、30 d氯胺酮组(K30d组)、30 d氯胺酮+胞二磷胆碱组(K+C30d组);360 d对照组(C60d组)、60 d氯胺酮组(K60d组)、60 d氯胺酮+胞二磷胆碱组(K+C60d组)。K14d组、K30d组、K60d组、K+C14d组、K+C30d组和K+C60d组均在生后第7天、第9天、第11天、第13天腹腔注射氯胺酮70 mg/kg,C14d组、C30d组和C60d组在出生7 d后,腹腔注射生理盐水(0.5 ml,1次/d,连续7d)。K+C14d组、K+C30d组、K+C60d组大鼠在腹腔注射氯胺酮后当天腹腔注射胞二磷胆碱500 mg/kg(0.5ml,1次/d,连续7 d)。大鼠分别在出生后14 d、30 d和60 d进行条件恐惧实验测试认知功能。结果:条件恐惧实验结果:条件关联和条件暗示测试中,在出生后第14天,K14d组和K+C14d组两组间的恐惧凝滞时间差异无统计学意义(P>0.05),但均短于C14 d组大鼠(P<0.05);在出生后第30天,K30d组短于C30d组和K+C30d(P<0.05),C30d组与K+C30d组差异无统计学意义(P>0.05);在出生后第60天,K60d组短于C60d组和K+C60d(P<0.05),C60d组与K+C60d组差异无统计学意义(P>0.05)。结论:多次氯胺酮(70 mg/kg)腹腔注射麻醉可引起幼期大鼠长期的学习记忆能力损害;胞二磷胆碱腹腔注射可抑制氯胺酮麻醉对幼期大鼠学习记忆能力的损害。

Objective： To explore the therapeutic effects of citicoline on ketamine-induced longer learning and memory injury. Methods ： 54 male PND7 rats were randomly divided into 9 groups ac- cording to postnatal age and measures： On postnatal day 14： Control group （C14d group）, ket- amine group （K14d group） and ketamine plus citicoline （K ＋ C14d group） ; On postnatal day 30： control group （ C3od group）, ketamine group （ K30d group）, ketamine plus citic01ine （ K ＋ C30a group） ; On postnatal day 60： control group （C60d group）, ketamine group （K60d group）, ket- amine plus citicoline （ K ＋ C60d group）. Kt4d , K30d , K60d, K ＋ C14d , K ＋ C30d , and K ＋ C6od groups were treated with 70 mg/kg Ketamine on the 7th, 9th, llth, and 13th postnatal day respectively. C14d .C30d and C60d groups were treated with NS （0.5 ml, once/day, keep 7 days）. And K ＋ C14d, K ＋ C30d, and K ＋ C60d groups were treated with citicoline （500 mg/kg,0.5 ml, once/day, keep 7 days） also at the same day of ketamine intraperitoneal injection. Fear conditioning was tested to determine the learning and memory abilities in rats at age of 14 d,30 d and 60 d. Results ： Contexttesting in Fear conditioning： no significant difference of freezing time was shown among K14a and K ＋ C14d groups, but the freezing time in both groups were much shorter than C14d group （P 〈 0.05）. And the freezing time in K3od group was remarkably shorter than C3od and K ＋ C3od groups （ P 〈 0.05） , but no significant difference was showed among C3od and K ＋ C30d groups. The similar pattern were observed in C60a , K6oa and K ＋ C6oa groups. Conclusion ： Multiple daily injections of ketamine may cause cognitive dysfunction in rats, tion of coticoline. which may be inhibited by intraperitoneal injec-