摘要
基于前额皮质神经元突触超微结构变化探讨抑郁、焦虑模型大鼠发病机制以及加味温胆汤的干预作用。方法 将56只SPF级雄性SD大鼠(180~200 g)随机分为正常对照组、抑郁模型组、焦虑模型组、抑郁中药组、焦虑中药组、抑郁西药组和焦虑西药组。分别采用慢性轻度不可预见性应激及天敌暴露应激制作大鼠抑郁及焦虑模型,其中正常对照组、抑郁模型组及焦虑模型组大鼠给予生理盐水灌胃,抑郁中药组、焦虑中药组给予12 g/kg加味温胆汤灌胃,抑郁西药组及焦虑西药组分别给予1.8 mg/kg百忧解及帕罗西汀灌胃。35 d后进行行为学检测及取材,通过电镜检测各组大鼠前额皮质神经元超微结构变化。结果 行为学数据显示,抑郁模型组大鼠水平运动次数、垂直运动次数以及总路程比正常对照组显著减少(P<0.05),加味温胆汤能显著改善模型大鼠抑郁行为表现(P<0.05),抗抑郁西药百忧解只对总路程有显著影响(P<0.05);焦虑模型大鼠水平运动次数、垂直运动次数以及总路程比正常对照组显著增加(P<0.05),加味温胆汤能改善垂直运动次数和水平运动次数(P<0.05),对总路程无显著影响,抗焦虑西药帕罗西汀能改善垂直运动次数,对其他无显著影响(P<0.05)。电镜结果显示,抑郁模型组较正常对照组前额皮质神经元突触前膜突触囊泡数量减少,突触间隙增大,部分间隙模糊,突触后膜致密物厚度降低、长度缩短,突触界面结构参数降低,而加味温胆汤能改善此变化;焦虑模型组较正常对照组前额皮质神经元突触超微结构以及突触界面结构参数变化与抑郁模型组基本一致,但加味温胆汤无显著影响。结论 研究发现,加味温胆汤对抑郁、焦虑模型大鼠前额皮质突触超微结构、界面参数的影响并不一致,加味温胆汤的抗抑郁机制与突触的超微结构变化密切相关,但其抗焦虑作用可能与突触的超微结构变化并无太大关联,详细机制还需进一步探讨。
Objective To explore the pathogenesis of depression and anxiety model rats based on the changes of synaptic ultrastructure of prefrontal cortex neurons and the intervention effect of Jiawei Wendan Decoction(加味温胆汤). Methods Fifty-six SPF male SD rats(180~200 g) were randomly divided into 7 groups which were normal group, depression model group, anxiety model group, anti-depression TCM group, anti-anxiety TCM group, anti-depression Western medicine group and anti-anxiety Western medicine group. The chronic mild unforeseeable stress and natural enemy exposure stress were applied respectively to build the depression model group and anxiety model group. Among these groups, rats in the normal group, the depression model group and the anxiety model group received saline by gavage. The rats in the anti-depression TCM group and the anti-anxiety TCM group received Jiawei Wendan Decoction(12 g/kg) by gavage. The rats in the anti-depression Western medicine group and the anti-anxiety Western medicine group received fluoxetine(1.8 mg/kg) and paroxetine by gavage respectively. After 35 days, behavioral scoring and sample collection were conducted to test the ultrastructure of neuronal synapse in prefrontal cortex under electron microscope. Result Behavioral data showed that the frequencies of horizontal movements and vertical movements and the total distance in the depression model group significantly decreased compared with those of the normal group(P<0.05) and Jiawei Wendan Decoction significantly improved the depressive behavior of rats(P<0.05). The anti-depression Western medicine fluoxetine only had a significant influence on the total distance(P<0.05) and the frequencies of horizontal movements and vertical movements and the total distance in the anxiety model group significantly increased compared with those of the normal group(P<0.05). Jiawei Wendan Decoction significantly improved the frequency of horizontal movements and vertical movements(P<0.05) but had little effect on the total distance. Anti-depression Western medicine paroxetine improved the frequency of vertical movements but had little effect on others(P<0.05). Under electron microscope, compared with that of the normal group, the amount of synaptic vesicles in presynaptic membrane of prefrontal cortical neurons decreased in the depression model group and the synaptic space became larger while some space was obscure. The thickness and length of postsynaptic density also decreased, and the structural parameters of synaptic interface decreased(P<0.01). Compared with those of the normal control group, the changes of synaptic ultrastructure and structural parameters of synaptic interface of prefrontal cortex neurons in the anxiety model group were basically the same as those in the depression model group, but Jiawei Wendan Decoction had no significant effect. Conclusion It is found that the effects of Jiawei Wendan Decoction on the ultrastructure and interface parameters of the prefrontal cortex of depression and anxiety model rats were not consistent. The anti-depression mechanism of Jiawei Wendan Decoction was closely related to the ultrastructural changes of the synapses, but its anti-anxiety effect might not be significantly related to the ultrastructural changes of the synapses. The detailed mechanism still needs to be further explored.
作者
张齐
何晓微
戴建业
范卫红
高月
武丽
ZHANG Qi;HE Xiaowei;DAI Jianye;FAN Weihong;GAO Yue;WU Li(Guangxi University of Chinese Medicine,Nanning 530200,Guangxi,China)
出处
《中华中医药学刊》
CAS
北大核心
2023年第8期114-117,I0027,共5页
Chinese Archives of Traditional Chinese Medicine
基金
国家自然科学基金项目(81760834,81960847)
广西科技计划项目(2019JJA140426)
广西高校中青年教师科研基础能力提升项目(2022KY0294)。
关键词
加味温胆汤
情志
双向调节
突触超微结构
Jiawei Wendan Decoction(加味温胆汤)
emotions
dual-directional regulation
ultrastructure of synapse
