CCK-8激活CCK-BR抑制戊四唑诱导的小鼠海马星形胶质细胞活化*

doi:10.3870/j.issn.1672-0741.25.02.005

摘要/Abstract

摘要： 目的探讨八肽胆囊收缩素(CCK-8)对戊四唑(pentylenetetrazole,PTZ)诱导的小鼠海马星形胶质细胞增殖、凋亡以及活化的作用及其可能机制。方法将小鼠海马星形胶质细胞随机分为对照组、PTZ诱导组、PTZ+CCK-8低剂量组、PTZ+CCK-8中剂量组和PTZ+CCK-8高剂量组。使用MTT法检测细胞增殖能力,流式细胞术检测细胞凋亡和周期,免疫荧光检测活化标志物IBA-1的表达,ELISA检测神经胶质纤维酸性蛋白(GFAP)和间隙连接蛋白43(CX43)表达水平,qRT-PCR和Western blot法分别检测CCK-AR和CCK-BR的mRNA和蛋白表达水平。以单独CCK-8处理为对照,使用proglumide(CCK受体抑制剂)和CCK-8同时进行处理,评价proglumide对CCK-8作用效果的逆转作用。结果与对照组比较,PTZ诱导组细胞增殖能力显著降低、凋亡率显著升高、G1期细胞占比显著升高、G2期细胞占比显著降低、GFAP和Cx43表达水平显著升高、CCK-BR的mRNA和蛋白表达水平显著降低;与PTZ诱导组相比,PTZ+CCK-8组细胞增殖能力显著升高、凋亡率显著降低、G1期细胞占比显著降低、G2期细胞占比显著升高、GFAP和Cx43表达水平显著降低、CCK-BR的mRNA和蛋白表达水平显著升高,且均呈CCK-8剂量依赖性。与单独使用CCK-8处理相比,联合使用proglumide处理能逆转CCK-8的作用。结论 CCK-8通过CCK-BR改善PTZ诱导的小鼠海马星形胶质细胞损伤,促进细胞增殖、降低凋亡并抑制其活化。

Abstract: Objective To investigate the effects of cholecystokinin(CCK)-8 on pentylenetetrazole(PTZ)-induced proliferation,apoptosis and activation of glial cells in the mouse hippocampus and its possible mechanisms. Methods First,the cells were randomly divided into control,PTZ-induced,PTZ+CCK-8 low dose,PTZ+CCK-8 middle dose and PTZ+CCK-8 high dose groups.MTT assay was used to detect cell proliferation.Flow cytometry was used to detect cell apoptosis and cell cycle.Immunofluorescence was used to detect the expression of activation marker GFAP.ELISA was used to detect the expression levels of GFAP and Cx43.qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of CCK-AR and CCK-BR respectively.Then,with CCK-8 treatment alone as the control,proglumide(a CCK receptor inhibitor)and CCK-8 were used for simultaneous treatment to evaluate the reversing effect of proglumide on the action of CCK-8. Results Compared to the control group,cell proliferation was decreased,apoptosis rate was increased,the proportion of G1 cells was increased,the proportion of G2 cells was decreased,IBA-1 expression was increased,GFAP and Cx43 expression was increased,and mRNA and protein expression of CCK-BR was decreased in the PTZ-induced group.Compared to the PTZ-induced group,cell proliferation was increased,apoptosis rate was decreased,the proportion of G1 cells was decreased,the proportion of G2 cells was decreased,GFAP and Cx43 expression was decreased,and mRNA and protein expression of CCK-BR was increased in the PTZ+CCK-8 group,and all of them were CCK-8 dose-dependent.Compared with the treatment with CCK-8 alone,the combined treatment with proglumide could reverse the effect of CCK-8. Conclusion CCK-8 improves PTZ-induced injury of mouse hippocampal astrocytes through CCK-BR,promotes cell proliferation,reduces apoptosis and inhibits their activation.

Key words: sepsis-associated encephalopathy, cholecystokinin-8, cholecystokinin receptor, astrocyte activation

中图分类号:

R742.1

施媛, 李明霞, 高珊, 付葵, 彭坚. CCK-8激活CCK-BR抑制戊四唑诱导的小鼠海马星形胶质细胞活化^*[J]. 华中科技大学学报（医学版）, 2026, 55(3): 333-339.

Shi Yuan, Li Mingxia, Gao Shan et al. Activation of CCK-BR by Cholecystokinin-8 Inhibits Pentylenetetrazole-induced Astrocyte Activation of the Mouse Hippocampus[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(3): 333-339.

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CCK-8激活CCK-BR抑制戊四唑诱导的小鼠海马星形胶质细胞活化^*

Activation of CCK-BR by Cholecystokinin-8 Inhibits Pentylenetetrazole-induced Astrocyte Activation of the Mouse Hippocampus

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