目的 观察甲状腺素( T4 )联合多奈哌齐对成年期甲状腺功能减退症(甲减)大鼠的海马内突触前膜相关蛋白1 (syntaxin-1)表达的影响,探讨甲减脑损伤及可能的恢复机制. 方法 44只SD大鼠随机分为4组:对照组、甲减组、T4替代治疗组及T4和多奈哌齐联合治疗组. 通过饮水给予丙基硫氧嘧啶0. 05%建立成年期大鼠甲减模型共6 周. 第5周开始,对照组腹腔注射等量生理盐水, T4替代治疗组每日给予左旋甲状腺素(L-T4) 6 μg/100 g 体重(BW)腹腔注射,联合治疗组每日给予6 μg/100g BW L-T4腹腔注射及饮用水中加入0. 005%多奈哌齐. 采用免疫组织化学法和West-ern blot法分析4 组大鼠海马syntaxin-1 的表达情况. 结果与对照组比较,甲减组大鼠血清三碘甲状腺原氨酸( T3 )、T4水平减低,促甲状腺激素(TSH)水平升高(P<0. 01),海马内syntaxin-1在CA1、CA3 各层及齿状区多形层( DG-PL)表达显著增加( P <0. 01 );T4 替代治疗后,血清 T3、T4 和TSH水平恢复至正常水平, syntaxin-1 蛋白的表达未完全恢复到对照组水平(P<0. 05);T4联合多奈哌齐治疗后syntax-in-1蛋白表达与对照组比较差异无统计学意义. 结论 T4联合多奈哌齐治疗可以修复成年期甲减导致的脑损伤.%Objective To observe the effects of thyroxine(T4) and donepezil on hippocampal syntaxin-1 expression in adult hypothyroidism rats, and clarify the possible mechanism under the hypothyroidism-induced cognitive dys-function. Methods The Sprague-Dawley rats were randomly classified into four groups:normal control, hypothy-roid(PTU:0. 05%, add to the dringking water), hypothyroid receiving levothyroxine replacement therapy(6 μg/100 g body weight once daily, ip injection) , and a combination of both drugs ( levothyroxine:6 μg/100 g;done-pezil 0. 005%). Serum T3, T4 and TSH concentrations were obtained using a radioimmunoassay kit. Protein levels of syntaxin-1 were determined by immunohistochemistry and Western blot. Results Compared to the control, the serum T3 and T4 levels of the hypothyroid group rats were significantly decreased, serum TSH elevated, syntaxin-1 in the hippocampus was significantly increased in CA1, CA3 and DG-PL regions. After levothyroxine or combined with donepezil treatment, serum T3, T4 and TSH were returned to the normal. But treatment with levothyroxine a-lone failed to normalize the expression of syntaxin-1 . The level of syntaxin-1 was restored completely to the control group. Conclusion Our findings suggest that adult-onset hypothyroidism may induce increment of syntaxin-1 in the hippocampus, which could be restored preferably by T4 combined with donepezil treatment.
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