低甲状腺素血症对发育期大鼠情绪影响的研究

Effect of hypothyroxinemia on the emotion in developing rats

目的 观察低甲状腺素血症对发育期大鼠情绪及海马神经元的影响.方法 69只健康1日龄（postnatal day,PD）大鼠随机分为对照组（n=36）和实验组（n=33）.PD1实验组大鼠行双侧甲状腺手术切除,制备低甲状腺素血症模型,对照组只暴露甲状腺而不切除.放射免疫法检测PD10、21、40血清T3、T4和促甲状腺激素（TSH）水平.PD30、31、32、33分别行悬尾实验、强迫游泳实验、高架十字迷宫实验、开场实验,测试大鼠的情绪变化.尼氏染色观察PD10、21、40海马CA1、CA3和DG区的存活细胞数.结果 实验组PD10、21、40血清T4水平均明显低于对照组,差异有统计学意义（P＜0.01）,血清T3、TSH水平差异无统计学意义（P＞0.05）.实验组悬尾实验静止时间（197.00±19.50）s,长于对照组（158.33±32.90）s,实验组强迫游泳实验静止时间（92.11 ±35.24）s,长于对照组（62.00±23.73）s,差异均有统计学意义（P＜0.05）.实验组高架十字迷宫入臂总次数和闭臂次数多于对照组（P＜0.05）,闭臂时间/总时间百分率少于对照组（P＜0.05）,开场实验组差异均无统计学意义（P＞0.05）.实验组PD10、21、40海马DG区的存活神经元数均明显少于对照组（P＜0.05）,而CA1和CA3区各日龄组差异均无统计学意义（P＞0.05）.结论 低甲状腺素血症可引起发育期大鼠抑郁情绪、活动增多及海马神经元的损伤.

Objective To investigate the effect of hypothyroxinemia on emotion and hippocampus neurons in developing rats. Methods Sixty-nine healthy postnatal day （PD） 1 rats were randomly divided into control group （n = 36 ） and experimental group （n = 33 ）. On PD1, experimental group was bilaterally thyroidectomized to establish hypothyroxinemia model, the control group was only given thyroid exposure operation without thyroid resection. On PD10,21,40, serum triiodothyronine （ T3 ）, thyroxine （ T4）, thyrotropic- stimulating hormone （TSH） were detected by radioimmunoassay. Tall suspension test, forced swimming test, the elevated-plus maze and open field were respectively employed to detect the anxiety/depression like behavior on PD30,31,32 ,33. Nissl＇s staining was used to determine the survival of neurons at PD10,21,40 in hippocampus CA1, CA3, DG regions. Results Serum T4 levels on PD10,21,40 in experimental group decreased significantly as compared with control group （P 〈 0. 01 ）, while there was no significant difference in serum T3 or TSH level （ P 〉 0.05 ）. In the tail suspension test, immobility time of experimental group [ （ 197. 00 ± 19. 50） s ] was longer than control group [ （ 158.33 ± 32. 90） s, P 〈 0. 05 ]. In the forced swimming test, immobility time of experimen- tal group [ （92. 11 ± 35.24 ） s ] was longer than control group [ （ 62. 00 ± 23.73 ） s, P 〈 0. 05 ] . In the elevated plus -maze test, total number of arm entries and closed arm entries in experimental group were increased as com- pared with control group（P 〈0. 05） ,percentage of closed arm/total time of experimental group was decreased as compared with control group （ P 〈 0. 05 ）. In the open field , there was no obvious difference between the two groups （P 〉 0.05 ）. On PD10,21,40, the amount of neurons in DG region of experimental group were less than control group（P 〈0. 05） ,while there was no significant difference in CA1 or CA3 on PD10,21,40（P 〉0.05）. Conclusions Hypothyroxinemia can cause depression, hyperactivity and hippocampus neuron damage of developing rats.