硫辛酸和左甲状腺素钠联合治疗对甲状腺功能减退大鼠认知功能和氧化应激的影响

目的：研究甲状腺素、硫辛酸及两药联合治疗对甲状腺功能减退大鼠认知功能损伤的改善，以及血清、海马组织中超氧化物歧化酶（ superoxide dismutase ， SOD）、丙二醛（ malondialdehyde ， MDA）的变化。方法成年SD雄性大鼠50只，每组10只，随机分为5组，对照组、甲减组丙硫氧嘧啶（PTU）组]、左甲状腺素钠（L-T4）组（PTU＋L-T4组）、硫辛酸（ LA）组（ PTU＋LA组）、联合用药组（ PTU＋L-T4＋LA组）。8周后以Morris 水迷宫试验检测大鼠空间学习记忆能力，采用黄嘌呤氧化酶法测定血清和海马组织SOD活力，采用硫代巴比妥酸法测定血清和海马组织MDA含量。结果与对照组比较，PTU组定位航向实验逃避潜伏期明显延长，差异有统计学意义（P＜0．05）；空间探索能力成绩降低，但差异无统计学意义；SOD 活性降低（P＜0．001），MDA 含量升高（P＜0．001）。与 PTU 组比较，PTU＋L-T4组、PTU＋LA组、PTU＋L-T4＋LA组大鼠逃避潜伏期均缩短，SOD 活力升高，MDA 含量降低（ P＜0．05）。结论 LA和L-T4联合治疗改善氧化应激，显著改善甲状腺功能减退大鼠的认知功能。

L-T4 and LA intervention prevents oxidative stress and cognitive deficit in experi-mental hypothyroid rats

Objective To assess the effect of levothyroxine , lipoic acid and their combination therapy on improving the cognitive deficit and on the level of oxidative stress in the serum and hippocampus tissue of adult hypothyroid rast .Methods Fifty male SD rats were randomly divided into five groups：normal group , hypothyroidism group propylthioaracil （ PTU ） group], the levothyroxine sodium （L-T4） treatment group （PTU ＋L-T4 group）, the lipoid acid（LA） treatment group （PTU＋LA group）, and the two-drug combination group （PTU＋LT-4＋LA group）.After 8 weeks of treatment, the learn-ing and memory abilities of the rats were evaluated by Morris Water Maze （ MWM ） .The content of malondialdehyde （ MDA） and the activities of superoxide dismutase （ SOD） in the serum and hippocampus were respectively measured using thiobarbituric acid ,and xanthine-xanthine oxidase methods .Results Compared with the normal group , the escape latency was longer（P〈0.01）, the MDA level was increased and the SOD activity was decreased in the serum and hippocampus in the PTU group （P〈0.001）.Compared with PTU group, the SOD activity was increased and the MDA level was decreased in the PTU ＋L-T4 group, PTU ＋LA group and PTU ＋L-T4 ＋LA group（P〈0.05）.There was significant difference in MWM test score .Conclusion The L-T4 and LA combination therapy can significantly improve the cognitive function of hypothyroid rats.