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目的旨在探讨伊潘立酮联合阿立哌唑对慢性铝暴露痴呆模型大鼠海马神经元及BDNF和NGF表达的影响。方法选择6周龄清洁级SD雄性大鼠建立慢性铝暴露痴呆模型,分为模型组、伊潘立酮组、阿立哌唑组和联合组,每组各20只,并同时设健康大鼠20只为对照组。伊潘立酮组大鼠接受0.05 g/ml伊潘立酮0.25 g/kg灌胃,阿立哌唑组大鼠接受0.05 g/ml阿立哌唑0.25 g/kg灌胃,联合组大鼠接受0.05 g/ml伊潘立酮0.25 g/kg和0.05 g/ml阿立哌唑0.25 g/kg灌胃,对照组大鼠和模型组大鼠均接受同等剂量生理盐水灌胃。各组大鼠均进行学习记忆测试和旷场实验测试。Annexin V/FITC法测定大鼠海马组织神经元凋亡率、RT-PCR法检测大鼠海马组织BDNF及NGF mRNA表达、Western blot法检测大鼠海马组织BDNF及NGF蛋白表达。结果对照组和联合组大鼠电击次数显著低于模型组大鼠(P<0.05),而水平穿越格数和竖立次数显著高于模型组大鼠(P<0.05)。联合组大鼠电击次数低于伊潘立酮组和阿立哌唑组大鼠,水平穿越格数和竖立次数高于伊潘立酮组和阿立哌唑组大鼠,但组间差异无统计学意义(P>0.05)。对照组、联合组、伊潘立酮组和阿立哌唑组大鼠海马组织神经凋亡率均显著低于模型组大鼠(P<0.05)。对照组、联合组、伊潘立酮组和阿立哌唑组大鼠海马组织BDNF及NGF mRNA、蛋白表达均显著高于模型组大鼠(P<0.01)。结论伊潘立酮联合阿立哌唑能显著抑制慢性铝暴露痴呆模型大鼠海马神经元凋亡,上调BDNF及NGF表达。
Objective To investigate the effect of iloperidone combined with aripiprazole on the expression of BDNF and NGF in the hippocampal neurons of chronic aluminum exposure dementia model rats. Methods Six-week-old SD male rats were randomly divided into model group, iloperidone group, aripiprazole group and combination group, with 20 rats in each group. Meanwhile, healthy SD rats 20 for the control group. Rats in the iloperidone group were treated with 0.05 g / ml iloperidone at a dosage of 0.25 g / kg. Rats in the aripiprazole group were treated with 0.25 μg / kg aripiprazole at 0.05 g / kg. The rats in the combination group 0.05 g / ml iloperidone 0.25 g / kg and 0.05 g / ml aripiprazole 0.25 g / kg were given orally. The rats in the control group and the model group received the same dose of normal saline. Rats in each group were subjected to learning and memory test and open field test. The apoptosis rate of hippocampal neurons in rat was measured by Annexin V / FITC method. The expression of BDNF and NGF mRNA in hippocampus was detected by RT-PCR. The expression of BDNF and NGF in hippocampus was detected by Western blot. Results The number of shocks in control group and combined group was significantly lower than that in model group (P <0.05), while the number of horizontal crossing and erection was significantly higher than that in model group (P <0.05). The number of shocks in the combined group was lower than that in the iloperidone group and the aripiprazole group, and the number of horizontal crossings and erection were higher in rats in the combination group than in the iloperidone group and the aripiprazole group Statistical significance (P> 0.05). The apoptotic rates of hippocampus in control group, combination group, iloperidone group and aripiprazole group were significantly lower than those in model group (P <0.05). The mRNA and protein expressions of BDNF and NGF in the hippocampus of the control group, the combination group, the iloperidone group and the aripiprazole group were significantly higher than those in the model group (P <0.01). Conclusion Ioperidone combined with aripiprazole can significantly inhibit the hippocampal neuron apoptosis and up-regulate the expression of BDNF and NGF in the rat model of chronic aluminum exposure dementia.