褪黑素对精神障碍大鼠星形胶质细胞极化的作用及机制研究  

Effect and mechanism of melatonin on astrocyte polarization in rats with mental disorder

作　　者：王原媛 李虎虎 庄丽丽 高鸿章 王聪 张召林 孙群书 WANG Yuan-yuan;LI Hu-hu;ZHUANG Li-li;GAO Hong-zhang;WANG Cong;ZHANG Zhao-lin;SUN Qun-shu(Department of Clinical Laboratory,Sunshine Ronghe Hospital,Weifang 261021;Laboratory of Jiangxi Zhonghong Boyuan Biotechnology Co.,LTD.,Nanchang 330200,China)

机构地区：[1]阳光融和医院检验科,山东潍坊261021 [2]江西中洪博元生物技术有限公司检验科,江西南昌330200

出　　处：《解剖科学进展》2024年第2期131-134,138,共5页Progress of Anatomical Sciences

基　　金：潍坊市卫生健康委员会科研项目(WFWSJK-2022-158)。

摘　　要：目的基于Nrf2-HO-1/CYP2E1通路探讨褪黑素调控精神障碍大鼠星形胶质细胞极化的作用机制。方法将50只大鼠随机分为假手术组、模型组、褪黑素组、Nrf2抑制剂(ML-385)组及褪黑素+ML-385组,采用刀片切割法损伤大鼠额叶皮质,复制精神障碍模型。糖水偏好和旷场实验检测大鼠行为学变化;HE和Nissl染色观察大鼠额叶皮质病理损伤和神经元损伤情况;免疫荧光染色检测大鼠额叶皮质GABA能神经元标记物GAD67、A1与A2型星形胶质细胞C3/GFAP与S100A10/GFAP表达;Western blot检测大鼠额叶皮质Nrf2-HO-1/CYP2E1通路相关蛋白Nrf2、HO-1、CYP2E1表达。结果与模型组相比,褪黑素组大鼠糖水偏好指数、跨格次数和站立次数显著提高,额叶皮质病理损伤减轻、神经元数量明显增加,大鼠额叶皮质GAD67表达水平显著升高、C3/GFAP表达水平显著降低、S100A10/GFAP表达水平显著升高,Nrf2、HO-1蛋白表达显著升高,CYP2E1蛋白表达水平显著降低;然而褪黑素对精神障碍大鼠的上述作用均被ML-385削弱或抑制。结论褪黑素可能通过调控Nrf2-HO-1/CYP2E1通路活性促进A1型星形胶质细胞向A2型极化,进而改善大鼠精神障碍状态。Objective To explore the mechanism of melatonin in regulating astrocytes polarization in rats with mental disorders based on Nrf2-HO-1/CYP2E1 pathway.Methods Fifty rats were randomly divided into sham group,model group,melatonin group,Nrf2 inhibitor(ML-385)group and melatonin+ML-385 group.The frontal cortex of rats were damaged by blade cutting to establish a mental disorder model.The behavioral changes of rats were detected by sucrose preference and open field experiment.The pathological damage and neuronal damage of the frontal cortex was observed by HE and Nissl staining.The expressions of GABAergic neuron marker GAD67,C3/GFAP and S100A10/GFAP in A1 and A2 type astrocytes were detected by immunofluorescence staining.The expressions of CXCR7,PI3K,Akt,p-PI3K and p-Akt proteins were detected by Western blot.Results Compared with the model group,the sugar water preference index,the number of crossing cells and the number of standing times of rats in the melatonin group were significantly increased,the pathological damage of the frontal cortex was alleviated,the number of neurons was significantly increased,the expression of GAD67 in the frontal cortex of rats was significantly increased,the expression of C3/GFAP was significantly decreased,and the expression of S100A10/GFAP was significantly increased,the expressions of Nrf2 and HO-1 protein were significantly increased,while the expression of CYP2E1 was significantly decreased.However,the above effects of melatonin on rats with mental disorders were weakened or inhibited by ML-385.Conclusion Melatonin might promote the astrocytes polarization of A1 to A2 by regulating Nrf2-HO-1/CYP2E1 pathway,and thus improve the mental disorders in rats.

关 键 词：精神障碍 褪黑素 星形胶质细胞 极化 Nrf2-HO-1/CYP2E1通路 

分 类 号：R749.5[医药卫生—神经病学与精神病学]