叶酸改善老年期轻度认知功能障碍大鼠学习记忆能力的机制

The mechanism of folic acid for improving the learning and memory abilities in elderly rats with mild cognitive impairment

目的探讨叶酸改善老年期轻度认知功能障碍(MCI)大鼠学习和记忆能力的机制。方法老年SD大鼠40只,随机等分为假手术对照组(SC)、模型对照组(MC)、低剂量给药组(LD)和高剂量给药组(HD)。造模后30 d起对LD组4 mg·kg-1·d-1、HD组12 mg·kg-1·d-1连续叶酸灌胃,SC组及MC组给予相同剂量生理盐水灌胃,30 d后分别检测其学习记忆能力、血清叶酸和同型半胱氨酸(Hcy)浓度、海马组织G蛋白偶联受体激酶2(GRK2)mRNA及蛋白表达。结果 HD、LD组学习记忆能力、血清叶酸浓度均高于MC组(P<0.05);HD、LD组血清Hcy浓度、GRK2mRNA及蛋白表达均低于MC组(P<0.05)。结论补充叶酸可以改善老年期MCI大鼠学习记忆能力,其机制可能与提高血清叶酸水平、降低血浆Hcy水平、减轻海马组织GRK2基因及蛋白表达有关。

To investigate the mechanism of folic acid on the improvement of learning and memory abilities in the elderly rat model of mild cognitive impairment.Methods Forty elderly SD rats were randomly divided into four groups including a sham-operated contorl(SC)group,a model control(MC)group,a low dose(LD)group and a high dose(HD)group(n=10 in each group).30 days after operation,LD group(low-dose folic acid 4 mg·kg-1 ·d-1 ) and HD group(high-dose folic acid 12 mg·kg-1 ·d-1 )were given intragastric administration with folic acid tablets dissovled in saline daily for 30 days.The rats in SC group and MC group were given intragastric administration with the same dose of saline daily also for 30 days.On the 30th day of intragastric administration,we measured the learning and memory abilities,serum folic acid and plasma homocysteine concentration,GRK2 mRNA and protein expression in hippocampal tissues.Results The learning and memory abilities and serum folic acid concentration in HD and LD groups were all significantly higher than those of MC group(P<0.05).The plasma homocysteine concentration and GRK2 mRNA and protein expression in HD and LD groups were all significantly lower than those of MC group(P<0.05).Conclusion Supplementation of folic acid can improve the learning and memory abilities of elderly MCI rats. The mechanism may be related with increasing serum folic acid concentration,reducing plasma homocysteine concen-tration and decreasing GRK2 gene and protein expression in hippocampal tissues.