摘要
目的:观察消退素D1(reslovin D1,RvD1)对Aβ诱导的小胶质细胞炎性激活和代谢紊乱的影响以及对阿尔茨海默病(Alzheimer’s disease,AD)转基因小鼠认知功能的影响。方法:培养小胶质细胞株BV2,予以脂多糖(LPS)、淀粉样蛋白(amyloidβ,Aβ)和RvD1处理,使用RT-PCR方法观察Nod样受体热蛋白结构域相关蛋白3(Nod-like receptor pyrin domain-containing protein 3,NLRP3)炎症小体的表达,使用共聚焦显微镜观察细胞线粒体形态学改变。通过给予AD转基因小鼠腹腔内连续10 d注射RvD1 5 mg/(kg·d),分别使用免疫组织化学染色(IHC)、免疫荧光(IF)、实时荧光定量PCR(RT-PCR)方法观察AD小鼠海马区NLRP3炎症小体通路、小胶质细胞标记物(Iba1)以及线粒体代谢调控相关因子的表达变化,并通过条件恐惧测试(FCT)探究其对于AD小鼠行为学的影响。结果:RvD1抑制了小胶质细胞NLRP3炎症小体激活。RvD1处理后小胶质细胞线粒体形态结构由异常的点状碎片状变为正常的条索状。RvD1治疗后,AD小鼠海马区NLRP3以及Iba1表达水平显著降低,同时线粒体代谢紊乱得到改善,并且认知功能得到恢复。结论:RvD1可能通过改善小胶质细胞线粒体代谢紊乱,抑制神经炎症,最终提高AD小鼠的认知功能。
Objective:To observe the effect of reslovin D1(RvD1)on Aβ-mediated inflammasome activation and metabolic disturbance of microglia and cognitive function in AD transgenic mice.Methods:Firstly,microglia(BV2 cell line)was cultured and treated with LPS,Aβand RvD1.By RT-PCR technique and confocal microscopy,we observed the activation of Nod-lide receptor pyrin domain-containing protein 3(NLRP3)inflammasome and changes of mitochondrial morphology,respectively.Moreover,continuous intraperitoneal injection of RvD1 5 mg/(kg·d)for 10 days was performed to AD transgenic mice.IHC,IF and RT-PCR were used to observe the activation of NLRP3 inflammasome,microglial marker(Iba1)and expression of mitochondrial metabolism-related factors.Ultimately,behavioral effect on AD mice was tested by fear conditioning test(FCT).Results:RvD1 inhibited the activation of the NLRP3 inflammation.After RvD1 applied,mitochondria morphology in microglia changed from dot fragment to strip shape.Compared with AD mice,AD mice treated with RvD1 revealed lower NLRP3 and Iba1 expression,improved mitochondrial metabolic disturbance in hippocampus and better cognitive function.Conclusion:RvD1 improves cognitive function in AD mice via alleviating the disturbance of mitochondria metabolism and inhibiting the activation of NLRP3 inflammasome in microglia.
作者
张本峥
张蒙
任怡稚
赵晓晶
张志远
Zhang Benzheng;Zhang Meng;Ren Yizhi;Zhao Xiaojing;Zhang Zhiyuan(Department of Pathology,School of Basic Medicine,Nanjing Medical University,Nanjing 210029,China)
出处
《南京医科大学学报（自然科学版）》
CAS
CSCD
北大核心
2019年第5期629-635,共7页
Journal of Nanjing Medical University(Natural Sciences)
基金
国家自然科学基金(81571240)
