摘要
目的观察甲状腺素(T4)联合多奈哌齐(DON)治疗对成年期甲状腺功能减退症(简称甲减)大鼠海马内超微结构及突触结合蛋白synaptotagmin-1(syt-1)表达的影响。方法饮0.05%丙基硫氧嘧啶(PTU)水建立成年期大鼠甲减模型共6周,第5周起,T4治疗组给予腹腔注射T4 6μg/100g体重、DON治疗组饮0.005%DON水,联合治疗组给予T4+DON治疗,对照组及甲减组每日腹腔注射等量生理盐水。采用放射免疫法测定血清甲状腺素水平,透射电镜观察海马内超微结构,Western blot方法分析海马内syt-1的表达水平。结果甲减组、DON治疗组大鼠血清甲状腺激素水平明显降低(P<0.01),T4治疗组、联合治疗组与对照组差异无统计学意义;电镜下甲减大鼠海马内神经元中线粒体呈现明显空泡变性、游离核糖体稀疏、突触结构受损、突触小泡数量减少,T4或DON治疗后上述损伤有所改善,而联合治疗恢复后表现最接近对照组;甲减大鼠海马内syt-1蛋白表达量明显降低(P<0.01),单独T4或DON治疗后表达仍下降(P<0.05),联合治疗后syt-1表达恢复正常。结论成年期甲减可致大鼠海马内超微结构发生病理学损害,syt-1蛋白表达下降,T4+DON治疗有利于上述损伤的修复,作用优于单一药物治疗。
Objective To investigate the effect of thyroxine（ T4） and donepezil（ DON） treatment on the hypothyroidism-induced alterations of ultrastructure and synaptotagmin-1（ syt-1） expression in the hippocampus of adult rats. Methods Administration of 0. 05% propylthiouracil（ PTU） to drinking water for 6 weeks was used to replicate the model of hypothyroidism. From the 5th week,T4 group was given thyroxine（ 6 μg /100 g body weight） by intraperitoneal injection,DON group was given 0. 005% DON in the drinking water,T4 ＋ DON group was given a combination of both,the control and hypothyroid groups were given the same volume of saline solution by intraperitoneal injection daily. The concentration of serum T3 and T4 was determined by radioimmunoassay kits,and the hippocampal ultrastructure was observed with transmission electron microscope（ TEM） and the protein level of syt-1 was measured by Western blot. Results Compared to the control group,the concentration of serum T3 and T4 was significantly decreased in the hypothyroid group and the DON group（ P〈0. 01）,but returned to the normal in the T4 group or combined with DON group. TEM revealed that signficant degeneration was in mitochondria and rarefaction in free ribosomes of adult hpothyroid rats,synaptic structural damage and reduction of synaptic vesicles also appeared. The ultrastructural was partly restored by T4 or DON administration,but was completely restored by a combination of both treatments. Expression of syt-1 protein was significantly lower in hypothyroid rats compared with the controls（ P〈0. 01）,and was still expressed at lower level in hypothyroid treated with T4 alone（ P〈0. 05）,while was restored to normal values after co-administation of T4 and DON. Conclusion These observations indicate that adult hypothyroidism induces ultrastructural damage and a decrease of syt-1 proten in the hippocampus,and the alterations can not be restored by T4 monotherapy. In addition,the co-administration of T4 and DON result in more effective restoration than either alone.
出处
《安徽医科大学学报》
CAS
北大核心
2015年第11期1547-1551,共5页
Acta Universitatis Medicinalis Anhui
基金
国家自然科学基金(编号:81272152)
