孕酮抑制Aβ诱导星形胶质细胞活化所致神经元损伤  

Progesterone protects neurons against impairment induced by Aβ activated astrocytes

作　　者：吴洁[1,2] 吴红海[1] 于洋[1] 秦亚彬[1] 韩晓磊[1] 侯艳宁[1,2] 

机构地区：[1]中国人民解放军白求恩国际和平医院药剂科,河北石家庄050082 [2]河北医科大学药理教研室,河北石家庄050017

出　　处：《中国药理学通报》2014年第11期1539-1543,共5页Chinese Pharmacological Bulletin

摘　　要：目的探究孕酮抑制Aβ诱导的星形胶质细胞活化,发挥神经元保护作用及其机制,为孕酮在阿尔采末病(Alzheimer’s disease,AD)防治中的应用提供实验依据。方法将原代培养的星形胶质细胞随机分为对照组、Aβ组及Aβ加3个浓度孕酮组,分别处理24 h后,与神经元共培养。MTT法检测神经元的存活率;ELISA检测条件培养液中炎症因子IL-1β和TNF-α的水平;免疫荧光法和Western blot检测星形胶质细胞NF-κB的活性。结果孕酮浓度依赖地抑制Aβ诱导的星形胶质细胞活化引起的神经元存活率下降;抑制Aβ诱导的星形胶质细胞IL-1β和TNF-α释放的升高;抑制Aβ诱导星形胶质细胞NF-κB的活性增加。结论孕酮通过抑制Aβ诱导的星形胶质细胞活化,发挥神经元保护作用,其作用机制可能与NF-κB信号通路有关。Aim To investigate the effect of progester-one （ PROG） in protecting the neurons against impair-ment induced by the Aβ1-42 activated astrocytes, and the underlying molecular mechanism. Methods The astrocytes were divided into 5 groups： control, Aβ, and Aβplus PROG groups treated with 3 different con-centrations of progesterone for 24h. Then, Aβand pro-gesterone were removed, and neurons were co-cultured with the treated astrocytes. MTT assay was used to e-valuate the viability of cultured neurons; ELISA was used to detect the levels of IL-1βand TNF-αin culture media of astrocytes; immunofluorescence and Western blot were performed to detect the activation of NF-κB in astrocytes. Results PROG dose dependently pro-tected against Aβ1-42 activated astrocytes induced via-bility decrease in co-cultured neurons. Aβ induced＆amp;nbsp;release of IL-1β and TNF-α from astrocytes, and in-crease of NF-κB activity was abolished by progesterone treatment. Conclusion PROG protects the neurons through inhibiting the reactivity of astrocytes, and the underlying mechanism involves the NF-κB signal trans-duction.

关 键 词：阿尔采末病 Β-淀粉样蛋白 星形胶质细胞 神经元 孕酮 TNF-α IL-1β 

分 类 号：R651.15[医药卫生—外科学]