脑室内注射同型半胱氨酸对大鼠行为的影响及其病理机制

目的 明确同型半胱氨酸(Hcy)对大鼠不同脑区的组织和细胞形态学作用及其对探究自主行为和学习记忆的影响.方法 将54只健康雄性Wistar大鼠按体重随机分为3组:阴性对照组、阳性对照组和Hcy处理组,每组18只.阴性对照组不进行任何处理,后两组采用脑室内注射的方法分别注射生理盐水和Hey(3 μmol).通过旷场实验和避暗实验观察在体情况下Hcy对动物行为和学习记忆能力的影响,通过HE染色、TUNEL法测定神经细胞凋亡及检测脑组织神经递质含量等实验,探讨Hcy对神经系统损伤的相关机制.结果 脑室内注射Hcy使动物在旷场实验中央格的停留时间(5.50±2.67)s]长于阳性对照组(2.13±1.36)a](t=3.375,P＜0.01),穿格数(15.50±8.12)、直立次数(4.63±2.45)与阳性对照组穿格数(27.63±11.45)和直立次数(11.50±5.81)相比均减少(t值分别为12.125和6.875,P值均＜0.05).Hcy组动物在避暗实验中的潜伏期(68.25 ±100.18)s]较阳性对照组(155.50±154.53)s]明显缩短(t=127.500,P＜0.05),错误次数分别为1.13±0.64和0.50±0.53.差异有统计学意义(t=0.750,P＜0.05).Hcy组动物脑室内注射Hcy导致皮层和海马出现明显组织形态学变化及神经细胞凋亡,皮层和海马组织中5-羟色胺、多巴胺和乙酰胆碱的含量低于阳性对照组.结论 脑室内注射Hcy引起的脑组织形态学改变、细胞凋亡和神经递质含量的变化可能与行为的改变密切相关,参与了Hcy导致脑功能损伤的机制.

The effects of intraventricular injection of homocysteine on the behavior of rats and the related mechanisms

Objective The brain damage induced by Hcy in vivo was investigated through observing the changes of brain histomorphology,spontaneous exploratory behavior,learning and memory function.Methods Fifty-four Wistar rats were randomly assigned to three groups as the following:negative control group(CT-),positive control group(CT+)and Hey treatment group(Hcy).Rats of the CT-were not treated with any measure.Rats of CT+ group and Hcy group were treated by intraventricular injection of saline and Hcy(3 μmol),respectively.Through open field test and step-through test,the behaviors of the rats were observed.Through HE staining,TUNEL experiments and determination of the brain neurotranamitter contents,the mechanisms of Hcy-induced brain damage were investigated.Results After intraventricular injection of Hcy,the rats'spontaneous exploratory behavior decreased and the learning and memory function was disordered.The latency of open field test in Hcy group(5.50±2.67)s]was longer than CT+ group (2.13±1.36)s](t=3.375,P＜0.01).Compared with the crossing times(27.63±11.45)and rearing times(11.50±5.81)in CT+ group,the crossing times(15.50±8.12)and rearing times(4.63±2.45)of Hcy group were significantly decreased(t=12.125,P＜0.05;t=6.875,P＜0.05).The latency of step-through test in Hcy group(68.25±100.18)s]was shorter than that in CT+ group(155.50±154.53)s](t=127.500,P＜0.05).The error frequency of Hcy and CT+ group were 1.13±0.64 and 0.50±0.53 respectively and the difference was significant(t=0.750,P＜0.05).Significant changes in the histomorphology and apoptoais neurons were observed in cerebral cortex and hippecampus tissue slices.Hcy treatment also decreased the contents of 5-HT,DA and ACh in cortex and hippocampus.Conclusion The changes in the histomorphology of cortex and hippocampus,apoptosis of neurons and the neurotransmitters may be the causes of behavior disorders.