甲状腺素联合多奈哌齐对成年期甲减大鼠海马SNAP-25的影响

Effects of thyroxine and donepezil on hippocampal SNAP-25 expression in hypothyroid adult rats

阐明甲状腺素联合多奈哌齐对成年期甲状腺功能减退症(简称甲减)大鼠海马突触小体相关蛋白25(SNAP-25)表达的影响,探讨成年甲减脑功能损伤及恢复机制。结果显示甲减大鼠血清T3、T4及海马CA1、CA3区和齿状回(DG)SNAP-25蛋白水平显著升高。单独甲状腺素或联合治疗后血清T3、T4水平恢复正常,但单独甲状腺素治疗后,海马SNAP-25水平仍显著高于对照组大鼠,联合治疗后海马各层SNAP-25蛋白水平与对照组无显著差异。这些结果提示,成年期甲减可致海马内SNAP-25蛋白表达增加,单独甲状腺素治疗后SNAP-25蛋白表达恢复不理想,与多奈哌齐联合治疗使甲减大鼠海马内SNAP-25蛋白恢复到正常水平。

We evaluated the effects of thyroxine and donepezil on hippocampal SNAP-25 expression in adult hypothyroidism rats, and clarified the possible mechanism under the hypothyroidism-induced cognitive dysfunction. Our data showed that the serum T3 and T4 levels were significantly lower in the hypothyroid group rats than those in the control group rats. After thyroxine or combined with donepezil treatment, serum T3 and T4 were returned to the normal. Compared to the control group, the immunoreactivity of SNAP-25 in CA1, CA3 and DG regions of hippocampus was significantly increased. A two-week treatment with T4 alone failed to normalize the expression of SNAP-25, however, there was no significant difference in SNAP-25 protein levels after coadministration of thyroxine and dozepezil. These results suggested that adult-onset hypothyroidism induced increment of SNAP-25 in the hippocampus, which could be restored by thyroxine combined with dozepezil treatment.