摘要
目的:探讨Amyloid beta(Aβ)通过激活核苷酸结合寡聚化结构域样受体3(NLRP3)炎症小体在湿性年龄相关性黄斑变性发病中的分子机制。方法:30只C57BL/6J小鼠按数表法随机分为对照组、实验1组与实验2组,每组各10只。实验1组与实验2组进行Aβ玻璃体腔注射,注入剂量为1μL(1μmmol/L)Aβ与10μL(1μmmol/L)Aβ,对照组玻璃体腔内注射等量生理盐水。检测小鼠视网膜功能与NLRP3炎症小体表达变化情况。结果:所有小鼠在注射后7 d与14 d的视网膜各层结构清晰、细胞排列整齐,未出现炎症细胞浸润与明显的组织结构紊乱。玻璃体注射后7 d与14 d,实验1组与实验2组的视网膜a波振幅、b波振幅均低于对照组,且实验2组低于实验1组(P<0.05)。实验1组与实验2组玻璃体中的IL-6、TNF-α值与NLRP3、Caspase-1蛋白相对表达水平高于对照组,且实验2组高于实验1组(P<0.05)。玻璃体注射后7 d与14 d,实验1组与实验2组眼球中的SOD活性低于对照组,且实验2组低于实验1组(P<0.05)。结论:Aβ可通过激活NLRP3炎症小体的表达,抑制SOD活性,诱发炎症因子的释放,从而在湿性年龄相关性黄斑变性发病中发挥重要作用。
Objective:To investigate molecular mechanism of the activation of NLRP3 inflammatory corpuscles by amyloid beta(Aβ)in the pathogenesis of wet age-related macular degeneration.Methods:30 cases of C57BL/6J mice were divided into three groups,the control group,experimental group 1 and experimental group 2,with 10 cases in each group.Experimental group 1 and group 2 were injected with Aβvitreous cavity,the injection dose were 1μl(1μmmol/L)Aβand 10μl(1μmmol/L)Aβ,and the control group were injected with the same amount of normal saline.The changes of mouse retinal function and expression of NLRP3 inflammatory bodies were detected.Results:All the retinal layers at 7 d and 14 d after vitreous injection were clear in all the mice,and the cells were arranged neatly.There were no inflammatory cell infiltration and obvious tissue structural disorder.At 7 d and 14 d after vitreous injection,the retinal a-wave amplitude and b-wave amplitude of the experimental group 1 and experimental group 2 were lower than those of the control group,and the experimental group 2 was lower than experimental group 1(P<0.05).The relative expression levels of IL-6,TNF-α,NLRP3,and Caspase-1 proteins in the vitreous of the experimental group 1 and the experimental group 2 were higher than those of the control group,and the experimental group 2 were also higher than the experimental group 1(P<0.05).At 7 d and 14 d after the vitreous injection,the SOD activity in the eyeballs of the experimental group 1 and the experimental group 2 were lower than that of the control group,and the experimental group 2 were also lower than that of the experimental group 1(P<0.05).Conclusion:Aβcan activate the expression of NLRP3 inflammatory corpuscles and induce the release of inflammatory factors,inhibit SOD activity,thus playing an important role in the pathogenesis of wet age-related macular degeneration.
作者
齐赟
高珊
史强
程育宏
QI Yun;GAO Shan;SHI Qiang;CHENG Yu-hong(Department of Ophthalmology,the First Affliated Hospital of Xi'an Jiaotong University,Xi'an 710061,Shaanxi,China)
出处
《川北医学院学报》
CAS
2020年第4期551-554,567,共5页
Journal of North Sichuan Medical College
基金
陕西省自然科学基础研究计划项目(2019JM-578)。
