甲状腺素联合多奈哌齐对成年期甲状腺功能减退症大鼠海马syntaxin-1的影响被引量：4

Effects of thyroxin and donepezil on hippocampal syntaxin-1 expression in adult rats with hypothyroidism

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摘要目的观察甲状腺素(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)6μg/100 g体重(BW)腹腔注射,联合治疗组每日给予6μg/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Western 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syntaxin-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.

作者李保山查小雪朱德发康冬梅

机构地区安徽医科大学附属省立医院老年内分泌科安徽医科大学第一附属医院老年内分泌科

出处《安徽医科大学学报》 CAS 北大核心 2015年第10期1390-1393,共4页 Acta Universitatis Medicinalis Anhui

基金国家自然科学基金(编号:81272152) 安徽省科技计划项目(编号:12010402134)

关键词甲状腺功能减退症甲状腺素多奈哌齐 syntaxin-1 海马 hypothyroidism thyroine dozepezil hippocampus

分类号 R581.2 [医药卫生—内分泌]

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