艾烟和香烟对APP/PS-1小鼠海马核苷酸结合寡聚结构域样受体蛋白3炎性小体的影响探讨  

The effect of moxa smoke and cigarette smoke on brain NLRP3 inflammasome in APP/PS-1 transgenic AD mice

作　　者：吴嘉威 王昊 刘雅洁 和蕊 何梦如 赵百孝[4] WU Jiawei;WANG Hao;LIU Yajie;HE Rui;HE Mengru;ZHAO Baixiao(Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学针灸推拿学院,100029 [2]北京中医药大学生命科学学院,100029 [3]中国人民解放军总医院第六医学中心针灸科 [4]北京中医药大学东直门医院针灸一科

出　　处：《环球中医药》2023年第5期852-858,共7页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(81574068)。

摘　　要：目的观察艾烟和香烟对淀粉样前体蛋白/早老素-1(amyloid precursor protein/presenilin-1,APP/PS-1)双转基因小鼠海马核苷酸结合寡聚结构域样受体蛋白3(NOD-like receptor protein 3,NLRP3)炎性小体表达的影响,从神经炎症角度探讨艾烟的相关作用机制。方法6月龄雄性APP/PS-1小鼠随机平均分成模型组、艾烟组、香烟组,并设6月龄雄性C57BL/6小鼠作为空白对照组,每组12只。艾烟组与香烟组分别用艾烟与香烟干预,烟雾浓度控制在5~15 mg/m 3之间,每日一次,每次20分钟,每周6次,共计8周。实验结束后,利用水迷宫比较各组小鼠学习记忆功能,利用蛋白质印迹法及免疫组化测量比较各组小鼠海马中NLRP3、半胱氨酸天冬氨酸蛋白酶1(cysteiny1 aspartate specific proteinase-1,Caspase-1)、Toll样受体4蛋白(toll-like receptor 4,TLR4)、白细胞介素-1β(interleukin-1β,IL-1β)蛋白水平表达含量及累积光密度值(integrated optical density,IOD)。结果在水迷宫空间探索实验中,相较于模型组而言,香烟组组小鼠穿越平台次数和平台区域游泳时间增加(P<0.05),艾烟组小鼠平台次数和平台区域游泳时间明显减少(P<0.05);与模型组相比,香烟组小鼠的NLRP3、Caspase-1、TLR4蛋白含量显著升高(P<0.05),IL-1β蛋白含量及IOD数值变化不显著;艾烟组小鼠NLRP3、Caspase-1、TLR4、IL-1β蛋白含量显著降低(P<0.05),IOD值显著降低(P<0.05)。结论艾烟可以降低TLR4启动信号表达,抑制NLRP3炎性小体激活,减少Caspase-1活化及IL-1β炎症因子释放,降低脑内炎症反应,缓解阿尔茨海默病的疾病进程;而香烟则加剧阿尔茨海默病脑内慢性炎症。Objective To observe the effect of moxa smoke and cigarette smoke on brain NLRP3 inflammasome in APP/PS-1 transgenic AD mice and explore the mechanism of neuroinflammation by moxa smoke in AD mice.Methods 6-month-old male APP/PS-1 transgenic AD mice were randomly divided into 3 groups:model group,moxa smoke group,and cigarette smoke group(n=12),while 6-month-old male wild-type C57BL/6 mice were collected as the control group(n=12).Mice in the smoke group was exposed to smoke whose concentration was controlled within 5~15 mg/m 3.All interventions were 20 minutes a day,6 times a week,for 8 weeks.The Morris water maze measured the learning and memory function in mice,and the levels of NLRP3,Caspase-1,TLR4 and IL-1βwere observed by Western blot and immunohistochemistry.Results In the space exploration experiment of Morris water maze,the times of crossing the platform and the swimming time in the platform area in the cigarette group were significantly increased(P<0.05),while the times of crossing the platform and the swimming time in the platform area in the moxa smoke group were significantly decreased(P<0.05);compared with the model group,the brain NLRP3,Caspase-1 and TLR4 levels in the cigarette smoke group were significantly increased(P<0.05),there was no significant difference between the model group and the cigarette smoke group on the value of IOD.While the levels of NLRP3,Caspase-1,TLR4 and IL-1βin the brain tissues in the moxa smoke group were significantly decreased(P<0.05)and the IOD value of the moxa smoke group was significantly decreased(P<0.05).Conclusion Compared with cigarette smoke,moxa smoke did not aggravate the pathological changes of AD,but could reduce the priming signal TLR4 and inhibit the expression of NLRP3 inflammasome relate protein,meanwhile decrease the expression levels of IL-1β,control neuroinflammation to alleviate the progress of AD.

关 键 词：阿尔茨海默病 艾烟 香烟 神经炎症 NLRP3炎性小体 

分 类 号：R245.81[医药卫生—针灸推拿学]