目的 建立多发性脑梗死痴呆(MID)模型,研究叶酸(A)与维生素B12(B)和维生素B6(C)联合使用对大鼠学习记忆功能的影响及可能的作用机制。方法 复方叶酸制剂组分单用、两两联合使用和三者联合使用试验。将SD大鼠随机分为假手术组、模型对照组、阳性对照组(甲磺酸双氢麦角毒碱片)、A组、B组、C组、AB组、AC组、BC组和ABC组,每组12只。研究叶酸与维生素B12和维生素B6对大鼠自体血栓注射所致MID模型学习记忆功能的影响。结果 与模型对照组相比,ABC组大鼠在第5天逃避潜伏期明显缩短(P<0.05)、穿越平台次数明显增多(P<0.05)、穿越目标象限次数显著增多(P<0.05)。结论 叶酸与维生素B12和维生素B6联合用药具有增效作用。作用机制可能通过保护海马神经细胞损伤,对认知功能减退达到改善作用,尤其对空间记忆障碍有较好的预防作用。
Abstract
OBJECTIVE To investigate the protective effects of folic acid (A) with vitamin B12 (B) and vitamin B6 (C) on the learning and memory impairment of multiple cerebral infarction dementia (MID) in rats and the potential mechanisms. METHODSE The compound folic acid preparation components were used alone, in combination with each other and in combination. SD rats were randomly divided into sham operation, model group, positive control group (co-dergocrine mesylate tablets), group A, group B, group C, group AB, group AC, group BC and group ABC. The effect of folic acid, vitamin B12 and vitamin B6 on learning and memory function of MID model induced by autologous thrombus injection in rats was studied. RESULTS Compared with the model group, the escape latency of the ABC group was significantly shortened on the 5th day (P<0.05), the number of crossing platforms was significantly increased (P<0.05), and the number of crossing target quadrants was significantly increased (P<0.05). CONCLUSION Folic acid combined with vitamin B12 and vitamin B6 has synergistic effect. The mechanism of action may be through the protection of hippocampal nerve cell damage, to improve cognitive function, especially to prevent spatial memory disorders.
关键词
叶酸 /
维生素B12 /
维生素B6 /
认知功能 /
脑卒中
{{custom_keyword}} /
Key words
folic acid /
vitamin B12 /
vitamin B6 /
cognitive function /
stroke
{{custom_keyword}} /
中图分类号：
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] ZHANG X M, ZHOU Y H, FAGN Z Z. Research progress of clinical application of folic acid [J]. Tianjin Pharm(天津药学), 2018, 30(3): 65-69.
[2] HUO Y, LI J P, QIN X H, et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China the CSPPT randomized clinical trial[J]. JAMA, 2015,313(13):1325-1335.
[3] EWA S, WESTLAW S, ARTUR R, et al. Is hyperhomocysteinemia a causal factor for heart failure? The impact of the functional variants of MTHFR and PON1 on ischemic and non-ischemic etiology[J]. Int J Cardiol, 2017, 228(2):37-44.
[4] IANG M, QIAN L, JIAGN Y W, et al. Genetically elevated circulating homocysteine concentrations increase the risk of diabetic kidney disease in Chinese diabetic patients[J]. J Cell Mol Med,2019,23(4):2794-2800.
[5] ZHANG M L, XIA L, XUE L J. The clinical value of homocysteine, folic acid and vitamin B12 on cognitive dysfunction in patients with ischemic stroke [J]. Med Sci J Cent South China(中南医学科学杂志), 2019, 47(5): 520-523.
[6] GAO Y L, ZHAO S G. Stroke and its risk factors and post-stroke cognitive impairment [J]. Med Recap (医学综述), 2014, 20(11): 2004-2006.
[7] HAN L Y, WU Q H, WANG C Y, et al. Homocysteine, ischemic stroke, and coronary heart disease in hypertensive patients: a population-based, prospective cohort study[J]. Stroke, 2015,46(7):1777-1786.
[8] HU Q T, TENG W H, LI J J, et al. Homocysteine and Alzheimer′s disease: evidence for a causal link from mendelian randomizational[J]. J Alzheimers Dis, 2016, 52(2):747-756.
[9] LOURDES C M G, DUSRTE R C F, SILVA M V F, et al. Hemostatic abnormalities in dementia: a systematic review and Meta-analysis[J]. Semin Thromb Hemost, 2019, 45(5): 514-522.
[10] ZHOU F T, CHEN S R. Hyperhomocysteinemia and risk of incident cognitive outcomes: an updated dose-response Meta-analysis of prospective cohort studies[J]. Ageing Res Rev, 2019, 51(5):55-66.
[11] ZHAO L, TANG K, GUO D J, et al. Retrospective analysis of folic acid application time in hyperhomocysteinemia patients[J]. Chin Pharm J(中国药学杂志), 2015, 50(10):905-908.
[12] LI G L, ZHANG C, CHEN L Y, et al. Effect of dipyridamole on learning and memory impairment in rat with vascular dementia[J]. Chin Pharm J(中国药学杂志),2018, 53(9):695-700.
[13] WANG Q, QIN W W, ZHANG J W. Effect of ferulic acid on learning and memory impairment by the repairing of mitochondrial fission-fusion imbalance in AD mice[J]. Chin Pharm J(中国药学杂志),2019, 54(9):703-710.
[14] SERITA T, FUKUSHIMA H, KIDA S. Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine desity and complexity[J]. Sci Rep, 2017, 7:425-428.
[15] PETRAS M, TATARKOVA Z, KOVALSKA M, et al. Hyperhomocysteinemia as a risk factor for the neuronal system disorders[J].J Physiol Pharmacol, 2014, 65(1):15-23.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(5450 KB)
