二甲胺四环素对小胶质细胞激活状态影响的研究  

The effect of minocycline on the activation state of microglia

作　　者：左安俊[1] 欧振飞 王天瑞[1] 丁磊[1] 李天予 于腾波[1] Zuo anjun;Ou zhenfei;Wang tianrui;Ding lei;Li tianyu;Yu tengbo(The Affiliated Hospital of Qingdao University,Department of Sports Medicine,Qin-gdao 266100,China)

机构地区：[1]青岛大学附属医院运动医学科,266100

出　　处：《中华老年骨科与康复电子杂志》2022年第3期152-158,共7页Chinese Journal of Geriatric Orthopaedics and Rehabilitation(Electronic Edition)

基　　金：国家自然科学基金资助项目(31872310)。

摘　　要：目的探究二甲胺四环素对大鼠小胶质细胞M1、M2激活状态的研究。方法取10只Wistar大鼠脑组织,选取其小胶质细胞,以LPS及IL-4产生M1激活组和M2激活组,确定Notch信号通路对小胶质细胞M1激活途径及M2激活途径的调控作用,通过不同浓度二甲胺四环素干预Notch信号通路,调控小胶质细胞的激活状态,观察细胞膜特异性抗原CD16/32及CD206蛋白表达和细胞培养上清中TNF-α、IL-12、IL-10水平。结果成功诱导M1激活组和M2激活组,确定Notch信号通路对M1激活途径及M2激活途径起调控作用,二甲胺四环素在0μg/ml、5μg/ml、10μg/ml、20μg/ml浓度中,促使小胶质细胞TNF-α、IL-12分泌逐渐减少,IL-10分泌逐渐增多,CD16/32蛋白表达逐渐降低,CD206蛋白表达逐渐增加。结论二甲胺四环素能够抑制小胶质细胞向M1型极化,且对M2型极化过程没有影响,可以改善脊髓损伤患者的预后。Objective To investigate the activation status of minocycline on microglia M1 and M2 in rats.Methods The brain tissue of 10 Wistar rats was used to select microglia cells,and LPS and IL-4 were used to produce M1-activated group and M2-activated group to determine the regulatory effect of Notch signaling pathway on M1-activated pathway and M2-activated pathway of microglia.The Notch sig-naling pathway was interfered with different concentrations of minocycline to regulate the activation state of microglia.The expression of cell membrane specific antigen CD16/32 and CD206 and the levels of TNF-α,IL-12 and IL-10 in cell culture supernatant were observed.Results The M1 activation group and M2 activa-tion group were successfully induced,and the Notch signaling pathway was determined to regulate the M1 activation pathway and M2 activation pathway.Minocycline promoted the secretion of TNF-αand IL-12 in microglia at 0μg/mL,5μg/mL,10μg/mL and 20μg/mL concentrations.The secretion of IL-10 increased gradually,the expression of CD16/32 decreased gradually,and the expression of CD206 increased gradually.Conclusion Minocycline can inhibit the polarization of microglia to M1-type and has no effect on M2-type polarization process,which can improve the prognosis of SCI patients.

关 键 词：二甲胺四环素 脊髓损伤 小胶质细胞 

分 类 号：R73[医药卫生—肿瘤]