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目的 探索利血平致慢性抑郁大鼠模型的合适剂量,观察不同剂量利血平对大鼠自发活动和体质量的影响,分析模型大鼠海马单胺类神经递质的变化特点.方法 60只大鼠随机分为5组,空白组,利血平0.3 mg/kg、0.4 mg/kg、0.5 mg/kg、0.6 mg/kg组,每组n=12;动物造模给予腹腔注射利血平注射液1次/d(按分组中的给药剂量给予),空白组给予同体积蒸馏水,连续用药14 d.分别对大鼠open-field得分和体质量进行测量,酶联免疫法检测大鼠海马单胺类神经递质的水平.结果 慢性腹腔注射利血平(0.5、0.6 mg/kg)可引起大鼠体质量减轻(P<0.01,P<0.05),0.4、0.5、0.6 mg/kg组出现抑郁样行为;0.3 mg/kg组体质量、open-field得分变化不明显.与空白组体质量[(278.75±4.65)]和抑郁open-field评分[(60.3±19.9)分]比较,0.5 mg/kg组14 d大鼠体质量[(256.17±4.89)g]与open-field行为评分[(43.4±8.4)分]差异有显著性(P<0.01).0.5 mg/kg利血平对7d组抑郁大鼠海马5-羟色胺(5-HT)含量有影响[(2.83±1.09) ng/ml,P<0.05],对14 d组5-HT含量无明显影响.与空白组比较,0.5 mg/kg组14d腹腔注射利血平对单胺类神经递5-羟色胺(5-HT)、多巴胺(DA)、去甲肾上腺素(NA)影响差异无统计学意义(P>0.05),但可见5-HT与NA含量呈显著负相关(r=-0.449,P<0.01).结论 慢性腹腔注射0.5 mg/kg利血平能引起大鼠抑郁样行为,利血平对海马单胺类神经递质的影响与用药时间相关.“,”Objective To observe the suitable dosage of reserpine for the establishment of rat model of depression and analyze the changes of monoamine neurotransmitter in hippocampus.Methods 60 rats were randomly divided into five groups:the normal group,the 0.3 mg/kg group,0.4 mg/kg group,0.5 mg/kg group and 0.6 mg/kg group,and 12 rats in each group.The model groups were intraperitoneally administrated by different dosage of reserpine (according to the dosage of the grouping) for 14 days and rats in the normal group were injected the same volume of solvent.The body weight was recorded at different days and activity was tested by openfield test at 0,7th and 14th day.Monoamine neurotransmitter changes in hippocampus were tested by enzymelinked immunosorbent assay.Results Reserpine could cause body weight loss (0.5,0.6 mg/kg) and depressive behavior (0.4,0.5,0.6 mg/kg).The group of 0.4 mg/kg showed no difference in weight and open-field test.Compared with the weight body ((278.75 ± 4.65) g) and open-field test (60.3 ± 19.9) at the model group,the group of 0.5 mg/kg at 14th showed significant differences in weight ((256.17 ±4.89) g) and behavior(43.4 ±8.4) (P<0.01).Dosage of 0.5 mg/kg had effect to 5-HT in hippocampus at 7th day ((2.83 ± 1.09) ng/ml,P<0.01) but not 14th day.Compare with the normal group at 14th day,the group of 0.5 mg/kg showed no difference at 5-HT,DA and NA,and there was significant negative correlation between 5-HT and NA(r=-0.449,P<0.01).Conclusion Reserpine of 5 mg/kg can result in the depressive behavior of rats.The effect of reserpine to monoamine neurotransmitter in hippocampus has relationship with time.