α-葎草烯调控NRG1/ErbB4信号通路改善精神分裂症研究

α-humulene improves schizophrenia via NRG1/ErbB4 signaling pathway

目的探讨α-葎草烯对小鼠精神分裂症的作用机制。方法采用地卓西平马来酸盐(MK801)建立精神分裂症小鼠模型,用不同浓度α-葎草烯进行ig给药。对各组小鼠进行旷场试验和前脉冲抑制(PPI)测试,评估小鼠自发活动量和感觉运动门控功能;检测小鼠额前脑组织NO活性、MDA含量;Westernblotting法检测小鼠海马组织NRG1、ErbB4蛋白表达水平。结果与对照组比较,模型组小鼠的活动量明显增加,PPI受损(P<0.01);脑内NO活性、MDA含量、NRG1、ErbB4蛋白表达显著增加(P<0.01)。与模型组比较,不同浓度α-葎草烯组中小鼠活动量明显降低,PPI异常明显改善,NO和MDA含量、NRG1和ErbB4蛋白表达均明显降低(P<0.05、0.01)。结论α-葎草烯通过下调NRG1/ErbB4信号通路,改善精神分裂症小鼠异常行为,从而达到治疗精神分裂症的目的。

Objective To study the treating mechanism ofα-humulene on the schizophrenic mice.Methods The schizophrenic models were established by dizocilpine maleate(MK801),then different concentrations ofα-humulene were used to treat the mice by intragastric administration.Open-field experiment and PPI test were carried out to evaluate the spontaneous activity and sensorimotor gating function of mice.Moreover,the frontal cortex MDA,NO levels and hippocampal NRG1,ErbB4 protein expression was detected.Results The spontaneous activity,sensorimotor gating function,MDA,NO,NRG1 and ErbB4 levels were significantly changed in model mice when compared with normal mice(P<0.01).Compared with model group,different concentrations ofα-humulene notably inhibited spontaneous activity,improved PPI value,increased NO and MDA content,down-regulated ErbB4 and NRG1 protein expression(P<0.05,P<0.01).Conclusion The schizophrenia abnormal behavior of mice was improved byα-humulene via down-regulating NRG1/ErbB4 signaling pathway,so as to achieve the purpose of treating schizophrenia.