左甲状腺素对淀粉样β蛋白所致痴呆模型小鼠空间学习记忆的影响

Effects of levothyroxine on spatial learning and memory deficiency of amyloid β-protein-induced dementia mice

目的探讨甲状腺激素对淀粉样β蛋白(Aβ)所致痴呆模型小鼠空间学习记忆的影响,并初步探讨其作用机制。方法小鼠海马内注射1.0μL的Aβ1-4210mmol·L-1制备阿尔茨海默病(AD)模型。小鼠一次性ip左甲状腺素(T4)5mg·kg-1后,Morris水迷宫实验测定对AD模型小鼠学习记忆的影响。分别采用比色法、黄嘌呤氧化酶法、碱性羟胺法和硫代巴比妥酸法检测小鼠海马胆碱乙酰转移酶(ChAT)和超氧化物歧化酶(SOD)活性,以及乙酰胆碱(ACh)和丙二醛(MDA)含量。结果与正常对照组比较,AD模型小鼠空间学习记忆能力受损。与AD模型组比较,T4治疗组小鼠在第3次到第6次训练中,在水迷宫中找到平台的时间明显缩短〔(105±9)vs(64±18)s;(90±11)vs(44±14)s;(71±14)vs(28±12)s;(65±11)vs(23±12)s〕;ChAT活性升高〔(21.9±6.7)vs(43.9±9.4)μmo.lg-1蛋白〕;SOD活性增高〔(2.40±0.12)vs(3.52±0.24)MU.g-1蛋白〕;ACh含量上升〔(4.74±0.60)vs(7.46±0.91)g.g-1蛋白〕;MDA减少〔(1.37±0.06)vs(0.74±0.09)μmol.g-1蛋白〕。结论T4可明显改善Aβ1-42所致痴呆模型小鼠空间学习记忆,其机制可能与增加脑内胆碱能神经功能,减少自由基损伤有关。

AIM To investigate the effects and mechanisms of thyroid hormones on spatial learning and memory deficiency of amyloid β- protein （Aβ） -induced dementia mice. METHODS Mice were injected intrahippocampally 1.0 μL Aβ1-4210 mmol·L^-1 to prepare dementia mice model. Levothyroxine （ l-thyroxinem, T4） 5 mg·kg^-1 were given ip to dementia mice, and the ability of learning and memory was examined by Morris water maze test. The activities of choline acetyltransferase （CHAT） and superoxide dismutase （SOD） were determined respectively by colorimetric method and xanthine oxidase method, the levels of acetylcholine （ ACh ） and malonic dialdehyde （MDA） were examined respectively by hydrox- ylamine colorimetric method and thiobarbituric acid method. RESULTS Compared with normal control group, the abilihy of spatial learning and memory was remarkably inpaired in the AD model mice. Compared with the dementia mice, the escape latency of T4-treated mice in water maze test was significantly shortened from the third to the sixth training [ （105 ± 9 ） vs （64±18）s;（90±11） vs （44 ±14）s;（71 ± 14） vs （28 ± 12） s; （65 ± 11） vs （23 ± 12） s3, the activities of ChAT [ （21.9 ± 6.7） vs （43.9 ±9.4）μmol·g^-1 protein3 and SOD [（2.40±0. 12） vs （3.52±0.24）MU·g^-1 protein）, and the level of Ach [（4. 74 ± 0.60） vs （7.46 ±0.91）g·g^-1 protein3 were increased, while the level of MDA （ （ 1.37 ± 0.06 ） vs （0.74 ±0.09） μmol·g^-1 protein was decreased in T4-treated mice. CONCLUSION The results of the present study suggested that T4 improve learning and memory defteieney of Aβ1-42-induced dementia mice. The mechanisms of T4 treating AD might be associated with increasing eholinergic function and protecting from the damage of free radicals in the brains of dementia mice.