郭育君 周旭辉 易新宇 杨俊 张雪花 侯超

摘要 目的：探討温胆汤通过接触蛋白相关蛋白3（CASPR3）对精神分裂症大鼠认知障碍的影响。方法：将SD大鼠随机分为正常组，模型组以及观察组，其中模型组大鼠腹腔注射MK-801 0.6 mg/kg诱导精神分裂症模型。观察组大鼠灌胃温胆汤20 mL/kg，模型组和正常组大鼠灌胃生理盐水20 mL/kg。采用刻板行为评分方法评定建模后5 min、10 min大鼠的刻板行为评分;采用谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）等试剂盒检测大鼠血清GSH-Px、CAT以及SOD的含量;采用TUNEL法检测大鼠大脑皮质神经元凋亡率;采用Morris水迷宫测试大鼠的学习记忆功能。采用Western blotting检测大鼠海马组织CASPR3蛋白的表达水平。结果：模型组大鼠在建模后5 min、10 min的刻板行为评分，平均逃避潜伏期，神经元凋亡率以及CASPR3蛋白表达较正常组升高（P<0.05），而观察组大鼠低于模型组（P<0.05）;模型组大鼠血清GSH-Px、CAT和SOD含量较正常组降低（P<0.05），而观察组高于模型组（P<0.05）。结论：温胆汤可改善大鼠的认知障碍，其作用机制可能与下调CASPR3蛋白的表达相关。

关键词 温胆汤;CASPR3;精神分裂症;认知障碍;氧自由基;凋亡

Wendan Decoction Improves Cognitive Disorder in Schizophrenic Rats through CASPR3

GUO Yujun1，ZHOU Xuhui1，YI Xinyu2，YANG Jun1，ZHNAG Xuehua1，HOU Chao1

（1 Department of Alcohol and Internet Addiction Psychiatry，Brain Hospital of Hunan Province，Changsha 410007，China; 2 Department of Chinese Traditional Rehabilitation Medicine，School of Medicine，Loudi Vocational and Technical College，Loudi 410007，China）

Abstract Objective：To explore the effect of Wendan Decoction on cognitive disorder in schizophrenic rats through contactin associated protein 3 （CASPR3）.Methods：SD rats were randomly divided into a normal group，a model group and an experimental group.In the model group，the rats were intraperitoneally injected with 0.6 mg/kg MK-801 to induce a schizophrenia model.The rats in the experimental group were intragastrically administrated with 20 mL/kg Wendan Decoction，and the rats in the model group and the normal group were intragastrically administrated with 20 mL/kg normal saline.The stereotyped behavior scoring method was used to evaluate the stereotyped behavior scores of the rats 5 and 10 min after modeling.Glutathione peroxidase （GSH-Px），catalase （CAT），superoxide dismutase （SOD） kits were used to detect rat serum GSH-Px，CAT and SOD content.The TUNEL method was used to detect the apoptosis of cerebral cortex neurons in rats.Morris water maze was used to test the learning and memory function of rats.Western blotting was used to detect CASPR3 protein expression in rat hippocampus.Results：The stereotyped behavior scores，average escape latency，neuronal apoptosis rate，and CASPR3 protein expression of rats in the model group were higher than those in the normal group at 5 min and 10 min after modeling （P<0.05），while those of the rats in the experimental group were lower than those in the model group （P<0.05）.The levels of serum GSH-Px，CAT and SOD in the model group were lower than those in the normal group （P<0.05），while those in the experimental group were higher than those in the model group （P<0.05）.Conclusion：Wendan Decoction can reduce the cognitive disorder of rats.Its mechanism may be related to the down-regulation of CASPR3 protein expression.

Keywords Wendan Decoction; CASPR3; Schizophrenia; Cognitive disorder; Oxygen free radical; Apoptosis

中图分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.06.012

精神分裂症（Schizophrenia，SCZ）是一种终身性疾病，全球人群患病率达1%，多发于青壮年;认知障碍是SCZ的一大核心症状，主要特征为工作学习记忆力下降，执行功能障碍，言语障碍等[1-2]。温胆汤是临床上用于“无形之痰”所致的精神疾病，具有理气化痰、和胃利胆的功效，已有研究表明其可改善SCZ大鼠学习记忆障碍、抗氧化损伤以及海马组织病理损伤等，对SCZ具有保护作用[3-4]。然而温胆汤改善SCZ大鼠认知障碍的机制尚不清楚。接触蛋白相关蛋白3（CASPR3）是一种神经细胞黏附因子，有研究发现其在新生小鼠基底神经节中表达，可参与调节大脑皮质的神经活动[5];既往研究表明CASPR3与SCZ的发生发展密切相关，其在SCZ患者中高表达，使用抗精神病类药物治疗后可恢复至正常水平[6]。……