左甲状腺素联合多奈哌齐对成年期甲状腺功能减退症大鼠的影响及机制探讨

摘要

Objective To investigate the effect and potential mechanism of levothyroxine combined with donepezil hydrochloride in adulthood hypothyroidism rats.Methods A total of 60 male SD rats was divided by random number table into group A,group B,group C and group D,15 rats in each group.The rats in group B,group,C and group D were treated with PLT to prepare hypothyroidism model,and group A was used as the control group.After successful preparation of the model,rats in group C and group D were injected intraperitoneally with levothyroxine(6 g/100 g) every day,and then group D was given another 0.005％ donepezil in drinking water.After 2 weeks,the learning and memory behavior of rats was observed by Morris water maze;the levels of serum T3 and T4 were measured by radioimmunoassay;the expression of syntaxin-1 in hippocampus was detected by immunohistochemistry and Western blot.Results The escape latency and swimming distance of rats were prolonged significantly in group B but shorted significantly in group C and group D,and swimming speed was significantly slowed in group B but significantly strengthened in group C and group D;the levels of T3 and T4 were obviously decreased in group B but increased significantly in group C and group D,especially in group D.The results of immunohistochemistry and Western blot showed that the expression level of syntaxin-1 in hippocampus of rats was lower in group B compared to control group but increased significantly in both group C and group D.Conclusion Levothyroxine combined with donepezil hydrochloride can improve the learning and memory ability in adult rats with hypothyroidism,and its mechanism is related to the increase of expression of synaptotagmin-1 in hippocampus.%目的 探讨左甲状腺素联合多奈哌齐对成年期甲状腺功能减退症大鼠的影响及可能机制.方法 SD雄性大鼠60只,按随机数字表分为A、B、C、D组,每组15只.其中B、C、D组大鼠均采取PLT制备甲状腺功能减退模型,A组作为正常对照.造模成功后C组和D组大鼠每日分别腹腔注射左甲状腺素(6μg/100 g),D组在C组的基础上给予在饮用水中加入0.005％多奈哌齐.2周后,采用Morris水迷宫观察大鼠学习记忆行为;用放射免疫法测定血清甲T3、T4水平;采用免疫组织化学法和West-ern blot法检测各组大鼠海马syntaxin-1的表达情况.结果 B组大鼠的逮避潜伏期和游泳路程明显延长,游泳速度明显变慢;C组和D组的逃避潜伏期和游泳路程明显缩短,游泳速度明显增快;B组的T3、T4水平明显降低.C组和D组的T3、T4水平明显升高,其以D组升高最明显.免疫组织化学法和Western blot法结果显示B组大鼠海马内syntaxin-1表达水平低于对照组,C组和D组大鼠海马内syntaxin-1表达水平明显升高.结论 左甲状腺素联合多奈哌齐可改善成年期甲状腺功能减退症大鼠的学习和记忆能力,其机制与升高海马组织syntaxin-1的表达有关.