Synaptotagmin 1在成年期甲减大鼠海马内表达变化及甲状腺素治疗效应  

Thyroid hormone regulates synaptotagmin 1 expression in the hippocampus of adult-onset hypothyroidism rats

作　　者：徐永霞[1] 王迅[1] 沈玉先[2] 朱德发[1] 

机构地区：[1]安徽医科大学第一附属医院老年内分泌科,合肥230022 [2]安徽医科大学教育部"重要遗传疾病基因资源利用"重点实验室(省部共建),合肥230032

出　　处：《安徽医科大学学报》2009年第6期670-673,共4页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:30772301);安徽省自然科学基金(编号:070413084)

摘　　要：目的研究成年期甲状腺功能减退症(甲减)大鼠海马突触小体内突触结合蛋白1(syt1)的表达量及甲状腺素替代治疗后的恢复状况,探讨甲减脑损伤及恢复的分子基础。方法用丙基硫氧嘧啶(PTU)建立成年期大鼠甲减模型,采用Western blot方法分析甲减组、小剂量甲状腺素替代治疗组、大剂量甲状腺素替代治疗组、正常对照组大鼠海马内syt1的表达情况。结果甲减组大鼠血清T3、T4水平显著低于正常对照组(P<0.05);背侧海马突触小体内syt1的蛋白表达水平显著低于正常对照组(P<0.05)。小剂量甲状腺素替代治疗后,血清T3、T4恢复至正常水平;syt1蛋白表达水平与甲减组比较未见明显改变(P>0.05)。经大剂量替代治疗后血清T3、T4高于正常;syt1的蛋白表达恢复到正常水平(P<0.05)。结论成年期甲减大鼠海马内syt1蛋白表达降低,甲状腺素治疗能使其恢复,且恢复的程度与甲状腺素的治疗剂量有关,大剂量替代治疗较小剂量效果好。Objective To observe the expression of synaptotagmin 1 （ syt 1 ） in hippocampus of adult onset hypothyroidism rats and the effect of Levothyroxin treatment. Further to explore the molecular mechanism of brain impairment by hypothyroidism. Methods All rats were separated into 4 groups randomly ： Hypothyroidism group （ Hypo, n = 12 ）, low dosage of L-T4 treated group （5-T4,n = 11 ）, high dosage of L-T4 treated group （20-T4, n = 11 ）, and control group （ CON, n = 11）. The level of syt 1 in hippocampus was analyzed by Western blot. Results In the Hypo group, the levels of serum T3 and T4 were significantly lower than those in the CON group （P 〈 0.05） ; and the level of syt 1 protein was significantly decreased in the crude synaptosome of dorsal hippocampus compared with the control group （P 〈 0. 05 ）. After giving administration of low dosage of L-T4, the levels of serum T3 and T4 were returned to normal, the level of syt 1 protein was ameliorated, but there was no significant alteration compared with the Hypo group. The high dosage of L-T4 could normalize the hypoexpression of syt 1 protein, while the levels of se- rum T3 and T4 were higher than the CON group. Conclusion Adult-onset hypothyroidism can decrease the expression of syt 1 in the dorsal hippocampus. L-T4 can reverse this alteration, and the high dosage of L-T4 is superior to the low dosage in restoring syt 1 expression.

关 键 词：甲状腺功能减退症/药物疗法 突触结合蛋白1 海马 甲状腺素/治疗应用 

分 类 号：R581.2[医药卫生—内分泌] R347.2[医药卫生—内科学]