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目的探究持续性叶酸缺乏饲料诱导高同型半胱氨酸血症(hyperhomocysteinemia,HHcy)大鼠海马CA3区神经元及大鼠行为学改变。方法 28只雄性SD大鼠随机分为叶酸缺乏组和对照组,叶酸缺乏组给予叶酸缺乏饲料,对照组给予正常饲料,饲养时间为6周。实验前后测定血清叶酸、同型半胱氨酸、超氧化物歧化酶浓度,旷场实验监测行为学改变。实验6周后,取叶酸缺乏组8只、对照组5只大鼠,麻醉后开胸经心腔用生理盐水及4%多聚甲醛灌注后取脑,分离海马,10%甲醛溶液固定后石蜡切片,行HE染色观察大鼠海马区神经元改变,其余大鼠直接麻醉后处死取海马组织并测定海马区脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)含量变化。结果与对照组比较,叶酸缺乏组大鼠体质量增长减慢,血清叶酸明显降低(P<0.001),同型半胱氨酸明显升高(P<0.001),且二者呈负相关(r=-0.717,P=0.000),血清SOD水平逐渐增高;叶酸缺乏组大鼠兴奋性减低,在新环境中出现紧张、焦虑等情绪改变,海马BDNF含量低于对照组(P<0.05)。结论叶酸缺乏所致的HHcy可致大鼠海马神经元形态及数目改变,并降低海马BDNF的表达,使大鼠出现抑郁样行为学改变。
OBJECTIVE: To investigate the behavioral changes of hippocampal CA3 neurons in rats with hyperhomocysteinemia (HHcy) induced by persistent folic acid deficiency. Methods Twenty-eight male Sprague-Dawley rats were randomly divided into folic acid deficiency group and control group. Folic acid deficiency group was given folic acid deficiency diet and control group was given normal diet for 6 weeks. The levels of serum folate, homocysteine and superoxide dismutase were measured before and after the experiment, and behavioral changes were monitored by open-field test. Six weeks after the experiment, 8 rats in folic acid deficiency group and 5 rats in control group were anesthetized, the brains were perfused with normal saline and 4% paraformaldehyde after anesthesia, and the hippocampus was separated. After fixed with 10% formaldehyde solution, paraffin The hippocampal neurons were observed by HE staining. The remaining rats were sacrificed and the hippocampus was sacrificed. The content of brain-derived neurotrophic factor (BDNF) in the hippocampus was measured. Results Compared with the control group, the folate deficient rats’ body mass growth slowed down, the serum folic acid was significantly lower (P <0.001) and the homocysteine was significantly higher (P <0.001), and both were negatively correlated (r = -0.717, P = 0.000). The level of serum SOD increased gradually. The excitability of the rats in folic acid deficiency group decreased. The stress and anxiety in the new environment were changed. The content of BDNF in the hippocampus was lower than that in the control group (P <0.05). Conclusions HHcy induced by folic acid deficiency can change the morphology and number of hippocampal neurons in rats and decrease the expression of BDNF in hippocampus, which may lead to depression-like behavioral changes in rats.