白藜芦醇改善亚临床甲状腺功能减退症大鼠的学习记忆能力及其可能机制

Resveratrol improves the impaired learning and memory in subclinical hypothyroidism rats and the possible mechanism

目的观察白藜芦醇(RES)对亚临床甲状腺功能减退(SCH)大鼠学习记忆能力的影响并探讨其可能机制。方法雄性成年SD大鼠,单侧甲状腺电凝毁损术建立SCH大鼠模型,随机分为模型组、RES(15 mg/kg)组及左旋甲状腺激素(LT4,60μg/kg)组,同时设假手术组,每组8只。灌胃给药2周后采用Morris水迷宫和Y迷宫观察大鼠学习记忆能力,放射免疫分析法检测大鼠血浆促甲状腺素(TSH)、游离甲状腺素(fT4)和三碘甲腺原氨酸(T3)浓度,Real-time PCR和Western blot方法观察大鼠海马中脑源性神经营养因子(BDNF)的表达。结果与假手术组比较,SCH大鼠血浆TSH浓度显著上升而T3和fT4浓度无明显改变,LT4(60μg/kg)和RES(15 mg/kg)灌胃给药均可降低SCH大鼠升高的TSH浓度但LT4组大鼠血浆fT4浓度也显著上升。与假手术组比较,SCH大鼠在Morris水迷宫和Y迷宫中的学习记忆能力显著下降,并且海马BDNF的mRNA及蛋白表达水平均显著降低。LT4(60μg/kg)和RES(15 mg/kg)灌胃给药2周可逆转SCH大鼠受损的行为学表现并增加BDNF在海马的表达。结论 RES可改善SCH大鼠的学习记忆能力,其机制与调控SCH大鼠失衡的甲状腺功能及海马BDNF表达有关。

Objective To investigate the effect of resveratrol （RES） on the learning and memory of subclinical hy- pothyroidism （SCH） rats and explore the possible mechanism. Methods A SCH rat model was established through hemi-thyroid electric coagulation, and the SCH rats were divided randomly into 3 groups including SCH model group, RES （ 15 mg/kg） group and levothyroxine （ LT4, 60 Ixg/kg） group. The rats in the sham group were only exposed thyroid without electric coagulation. 2 weeks after operation, all the 32 rats received a daily intragas- tric administration of sterile saline solution, RES or LT4 with the corresponding dose. The learning and memory a- bilities of the rats were tested using Morris water maze （MWM） and Y maze. The plasma concentrations of thyro- tropic-stimulating hormone （TSH）, free thyroxine （iT4）, and thiiodothyronine （T3） were detected using ELISA and radioimmunoassay method, respectively. The mRNA and protein expression of brain-derived neurotrophic factor （BDNF） was measured via real-time PCR and western blot method, respectively. Results The SCH rat model was successfully duplicated, as indicated by the elevated plasma thyrotropie-stimulating hormone （TSH） level with no changes of free thyroxine （fF4） and triiodothyronine （T3） concentration. Both RES （15 mg/kg） and LT4 （60 p^g/kg） could decrease the TSH concentration. Moreover, treatment with LT4 resulted in the increase of plasma IT4 level, In the MWM task and the Y maze task, the spatial learning and memory of the SCH rats were impaired compared with the sham ones. However, these changes were reversed by the treatment of RES （15 mg/kg） or LT4 （60 ~g/kg）. Furthermore, RES treatment up-regulated the mRNA and protein expression levels of BDNF in the hippoeampus. Conclusion These findings suggest an amelioration effect of RES on the impaired spatial learning and memory in SCH rats, the mechanism of which might be involved with its modifying effect on the imbalance of the thyroid function and the hippoeampal expression of BDNF.