成年期甲状腺功能减退症大鼠海马乙酰胆碱的变化

摘要

目的 研究成年期甲状腺功能减退症(甲减)大鼠海马内乙酰胆碱(ACh)含量、乙酰胆碱酯酶(AChE)活性变化,探讨成年期甲减引起认知功能损伤及其康复机制.方法 丙基硫氧嘧啶诱导成年期甲减大鼠模型,并给予左甲状腺素(L-T4)、乙酰胆碱酯酶抑制剂(多奈哌齐,DON)或L-T4联合DON干预后,测定大鼠血清T3 、T4和促甲状腺素释放激素(TSH)水平和海马内ACh含量及AChE活性.结果 甲减大鼠血清T3、T4水平显著减低、TSH水平增加(P＜0.05),L-T4、DON或L-T4+DON治疗后,甲减大鼠血清T3、T4、TSH均恢复至正常水平；甲减大鼠海马内ACh含量和AChE活性显著降低(P＜0.05),L-T4治疗后大鼠海马内ACh含量和AChE活性恢复正常,DON治疗后大鼠海马内ACh含量恢复到正常水平,但AChE活性仍显著降低(P＜0.01),L-T4+ DON治疗后,大鼠海马内ACh含量有升高趋势,但AChE活性显著降低(P＜0.05).结论 成年期大鼠甲减时海马内ACh含量降低,AChE活性被抑制,T4联合DON可提高甲减大鼠海马胆碱能系统活性.%Objective To study the acetylcholine(ACh) concentration and the acetylcholinesterase(AChE)activity in hippocampus of hypothyroid adult rats,and clarify the mechanism of cognition dysfunction under hypothyroidism in adult rats.Methods The hypothyroid adult rats were induced by adding 6-n-propyl-2-thiouracilin drinking water,and received the treatments.The levels of serum T3,T4,thyrotrophin-releasing hormone (TSH),and the ACh concentration and AChE activity in hippocampus were assayed.Results The levels of serum T3,T4 decreased with the increase of serum TSH (P ＜ 0.05),and the serum T3,T4,and TSH levels returned to nornal state after the Levothyroxine(L-T4) replacement therapy,AChE inhibitor donepezil (DON),or concentration of the L-T4 and DON treatment in hypothyroid adult rats.The ACh concentration and AChE activity in hippocampus decreased in adult-onset hypothyroidism(P ＜ 0.05),the ACh concentration and AChE activity recovered to the control rats after the L-T4 treatment.In addition,DON treatment reversed the ACh concentration to normal,however,the AChE activity was still inhibited(P ＜ 0.01).When combination of L-T4 with DON to treat the hypothyroid rats,the ACh concentration in hippocampus had a tendency to increase with the low activity of AChE (P ＜ 0.05).Conclusion The ACh concentration of hippocampus is decreased,and the AChE activity is inhibited,the combination of L-T4 and DON could improve the activity of hippocampus cholinergic system in hypothyroid rats.