合欢花黄酮对精神分裂症大鼠学习记忆能力、海马组织c-fos蛋白和基因表达水平的影响分析

Effects of Flos Albiziae flavonoid on the ability of learning and memory of schizophrenia rats and the expression of c-fos protein and gene in their hippocampus

目的 探讨合欢花黄酮对精神分裂症大鼠学习记忆能力、海马组织c-fos蛋白和基因表达水平的影响。方法 将72只SD大鼠随机分为对照组、模型组和合欢花黄酮高、中、低剂量组和氯氮平组各12只。合欢花黄酮高、中、低剂量组分别灌胃5 ml/kg合欢花黄酮(120 mg/kg、60 mg/kg和30 mg/kg),氯氮平组灌胃氯氮平(20 mg/kg),连续28d,在最后一次给药2 h后,模型组、合欢花黄酮高、中、低剂量组和氯氮平组分别给予一次性腹腔注射0. 6 mg/kg地佐环平/地卓西平(MK-801)建立大鼠精神分裂症模型,对照组给予等体积生理盐水。采用Morris水迷宫检测各组大鼠的学习记忆能力;HE染色观察大鼠的海马组织病理变化;TUNEL法检测海马组织神经元细胞的凋亡;逆转录-聚合酶链反应(RT-PCR)检测c-fos的表达;Western Blot检测c-fos、活化的含半胱氨酸的天冬氨酸蛋白水解酶3(Cleaved Caspase-3)、B细胞淋巴瘤/白血病-2(Bcl-2)和Bax的表达。结果 与对照组相比,模型组大鼠学习记忆能力明显下降(P <0. 05),海马组织细胞的凋亡率明显升高(P <0. 05),Bcl-2蛋白的表达明显下调(P <0. 05),c-fos、cleaved Caspase-3和Bax表达明显上调(P <0. 05);与模型组相比,合欢花黄酮高、中剂量组和氯氮平组大鼠学习记忆能力明显升高(P <0. 05),海马组织Bcl-2表达明显上调(P <0. 05),c-fos、cleaved Caspase-3和Bax蛋白的表达明显下调(P <0. 05);HE染色显示,合欢花黄酮高、中剂量组和氯氮平组大鼠海马组织病理变化明显减轻。结论 合欢花黄酮可以呈浓度依赖性的下调c-fos的表达,改善精神分裂症大鼠的学习记忆能力,减轻脑组织损伤。

Objective To explore effects of Flos Albiziae flavonoid(FAF)on the ability of learning and memory of schizophrenia rats and the expression of c-fos protein and gene in their hippocampus.Methods 72 SD rats were randomly divided into control group,model group,low-dose,medium-dose and high-dose FAF group and clozapine group,12 cases in each group.The rats in high-dose,medium-dose and low-dose FAF groups were intragastrically administered with 5 ml/kg FAF(120 mg/kg,60 mg/kg,30 mg/kg),while the rats in clozapine group were intragastrically administered with clozapine(20 mg/kg).2 h after the last administration,rats in model group,high-dose,medium-dose and low-dose FAF group and clozapine group were given one-time intraperitoneal injection of 0.6 mg/kg Dizocilpine/dizocilpine maleate to establish schizophrenia rat models.The rats in control group were given equal volume of normal saline.Morris water maze was used to detect learning and memory ability of rats in each group.HE staining was used to observe pathological changes of hippocampus.The apoptosis of hippocampus neurons was detected by TUNEL method;the expression of c-fos was detected by RT-PCR;and the expression of c-fos,cleaved Caspase-3,Bcl-2 and Bax were detected by Western Blot.Results Compared with control group,the rats'ability of learning and memory in model group was significantly decreased(P<0.05),while the apoptosis rate of hippocampus cells was significantly increased(P<0.05),the expression of Bcl-2 protein was significantly down-regulated(P<0.05),and the expression of C-fos,cleaved Caspase-3 and Bax were significantly up-regulated(P<0.05).Compared with the model group,the rats'ability of learning and memory in high-dose and medium-dose FAF group and clozapine group were significantly increased(P<0.05),the expression of Bcl-2 in hippocampus were significantly up-regulated(P<0.05),the expression of c-fos,cleaved Caspase-3 and Bax protein were significantly down-regulated(P<0.05).HE staining showed that pathological changes of hippocampus in high-dose and medium-dose FAF group and clozapine group were significantly alleviated.Conclusion FAF can down-regulate the expression of c-fos in a concentration-dependent manner,improve the learning and memory ability of schizophrenia rats,and alleviate brain tissue damage.