温胆汤对精神分裂症模型大鼠行为学及其海马组织PSD-95、GAP-43、JIP-3、Cx-43表达的影响

Effect of Wendan Decoction(温胆汤)on Expression of PSD-95,GAP-43,JIP-3,and Cx-43 in Hippocampus and Behaviors of Rats with Schizophrenia

目的:研究温胆汤对精神分裂症模型大鼠行为学及其海马神经元突触后致密蛋白95(PSD-95)、生长相关蛋白43(GAP-43)、JNK相互作用蛋白3(JIP-3)、连接蛋白43(Cx-43)表达的影响。方法:将SD大鼠随机分为:正常对照组、模型对照组、氯氮平0.02 g/kg组、温胆汤10、20、40 g/kg组。正常对照组和模型对照组分别灌胃生理盐水,各组分别灌胃相应药物,1次/d,连续给药21 d。末次给药2 h后,除正常对照组外,其余各组一次性腹腔注射MK-8010.6 mg/kg,以诱发精神分裂症模型。造模后,观察记录各组大鼠的行为学改变和刻板行为评分,旷场实验评价大鼠滞留时间及穿越次数;RT-q PCR法检测大鼠海马组织Psd95、Gap43、Jip3、Cx43 m RNA表达;WB法检测大鼠海马组织PSD-95、GAP-43、JIP-3、Cx-43蛋白表达。结果:与正常对照组比较,模型对照组大鼠刻板行为评分显著升高,在中央区滞留时间及穿越次数显著下降(P<0.01);其海马组织Psd95、Gap43、Jip3、Cx43 m RNA和蛋白表达显著下调(P<0.01);与模型对照组比较,温胆汤10、20、40 g/kg组均能明显降低大鼠刻板行为评分,明显升高中央区滞留时间及穿越频次(P<0.05或P<0.01);能明显上调海马组织Psd95、Gap43、Jip3、Cx43 m RNA和蛋白的表达(P<0.05或P<0.01)。结论:温胆汤可能通过上调PSD-95、GAP-43、JIP-3、Cx-43等突触相关蛋白的表达,从而调控海马神经元突触可塑性,缓解刻板行为和紧张、焦虑等情绪,增强学习和记忆功能,有效改善精神分裂症的认知障碍。

Objective:To explore the effect of Wendan Decoction(温胆汤)on expression of postsynaptic density protein-95(PSD-95),growth associated protein-43(GAP-43),c-Jun NH2-terminal kinase-interacting protein-3(JIP-3),and connexin-43(Cx-43)in hippocampal neu-rons and behaviors of rats with schizophrenia.Methods:SD rats were randomized into normal control group(normal saline,ig,once/day,21 days),model control group(normal saline,ig,once/day,21 days),0.02 g/kg clozapine group(ig,once/day,21 days),and 10,20,and 40 g/kg Wendan Decoction groups(ig,once/day,21 days).The 0.6 mg/kg MK-801 was injected(ip)into rats 2 h after the last ad-ministration except for normal control group to induce schizophrenia.After modeling,the behavioral changes and the stereotyped behavior scores of rats were observed and recorded.Open field test was conducted to observe the resting time and number of crossings.The m RNA ex-pression of Psd-95,Gap-43,Jip-3,and Cx-43 in rat hippocampus was detected by RT-q PCR,and protein expression of PSD-95,GAP-43,JIP-3,and Cx-43 in rat hippocampus by Western blotting.Results:Compared with the normal control group,the model group had high stereotyped behavior score,short resting time and small number of crossings in open field test(P<0.01),and low mRNA and protein expression of Psd-95,Gap-43,Jip-3,and Cx-43(P<0.01).Compared with the model control group,40,20,and 10 g/kg Wendan Decoction all re-duced the stereotyped behavior score,prolonged the resting time,increased the number of crossings(P<0.05 or P<0.01),and up-regulated the m RNA and protein expression of PSD-95,GAP-43,JIP-3,and Cx-43 in hippocampus(P<0.05 or P<0.01).Conclusion:Wendan De-coction increases the expression of synapse-related proteins PSD-95,GAP-43,JIP-3,and Cx-43,regulates synaptic plasticity of hippocampal neurons,alleviates the stereotyped behavior and behavioral changes such as tension and anxiety,and enhances learning and memory func-tions,which thus effectively relieves cognitive impairment in schizophrenia.