N-乙酰半胱氨酸对牙周炎伴阿尔兹海默病小鼠脑部炎症的抑制作用

Inhibitory effects of N-acetyl-L-cysteine on brain inflammation in mice with periodontitis and Alzheimer’s disease

目的通过阿尔兹海默病(Alzheimer’s disease,AD)小鼠的实验性慢性牙周炎(chronic periodontitis,CP)模型,研究牙周炎对AD小鼠脑部的影响,及N-乙酰半胱氨酸(N-acetyl-L-cysteine,NAC)对牙周炎伴AD小鼠的牙周和脑的影响。方法使用野生型C57小鼠10只作为空白组(C57组),使用3月龄APP/PS1转基因小鼠40只,随机分为牙周炎组(AD+CP组)、牙周炎+抗氧化组(AD+CP+NAC组)、抗氧化组(AD+NAC组)和单纯AD组(AD组)。AD+CP组、AD+CP+NAC组采用丝线结扎法建立牙周炎模型,同期对AD+CP+NAC组、AD+NAC组腹腔注射NAC(200 mg/kg),3周后取材观察牙槽骨高度、脑部海马区细胞形态,ELISA法检测海马中NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎症小体和β淀粉样蛋白(amyloid beta-protein,Aβ)、海马及牙龈中白细胞介素(IL)-1β、IL-18含量。结果与AD组相比,AD+CP组的牙槽骨吸收高度明显增加(P<0.05),牙龈中的IL-18、海马中的IL-1β、NLRP3含量明显升高(P<0.05)。与AD+CP组相比,AD+CP+NAC组牙槽骨吸收高度明显降低(P<0.05),牙龈中的IL-1β、IL-18含量明显降低(P<0.05),海马中的IL-1β、Aβ含量明显降低(P<0.05)。AD+CP组海马区神经细胞较C57组排列更加松散混乱,并有小胶质细胞的激活增多现象,而AD+CP+NAC组细胞排列混乱程度较AD+CP组轻。结论牙周炎可加重AD小鼠的脑部炎症,NAC可有效减少牙周炎引起的AD小鼠的牙槽骨吸收,降低牙龈和海马炎症因子水平,减少海马区神经细胞损伤。

Objective To explore the effects of periodontitis on the brains of Alzheimer’s disease(AD)mice and the effects of N-acetyl-L-cysteine(NAC)on the periodontium and the brain of AD mice with experimental chronic periodontitis(CP).Methods Ten wild-type C57 mice were in the blank control group(Group C57),and another 403-month-old APP/PS1 transgenic mice were randomly divided into four groups:AD+CP group,AD+CP+NAC group,AD+NAC group,and AD group.The periodontitis model was established in mice in AD+CP group and AD+CP+NAC group by silk ligation.At the same time,mice in AD+CP+NAC group and AD+NAC group were injected with NAC(200 mg/kg).The height of alveolar bone loss was detected after 3 weeks,and the cell morphology of the hippocampus was observed.We determined the expression levels of NLRP3 inflammasome and amyloid-β(Aβ)in the hippocampus as well as the expression levels of interleukin(IL)-1βand IL-18 in the hippocampus and gums by ELISA.Results Compared with AD group,the height of alveolar bone loss in AD+CP group was higher(P<0.05),and the expression levels of IL-18 in the gum and IL-1βand NLRP3 in the hippocampus were increased significantly(P<0.05).In addition,compared with AD+CP group,the height of alveolar bone loss in AD+CP+NAC group was reduced significantly(P<0.05),the expression levels of IL-1βand IL-18 in the gum werereduced significantly(P<0.05)as well as the expression levels of IL-1βand Aβin the hippocampus were reduced significantly(P<0.05).Compared with C57 group,the neurons in the hippocampus of AD+CP group were more loose and disordered,and the activation of microglia was increased,while the disarrangement of cells in AD+CP+NAC group was less than that in AD+CP group.Conclusion Periodontitis can aggravate brain inflammation in AD mice.NAC can effectively reduce alveolar bone resorption in AD mice caused by periodontitis as well as reduce the levels of inflammatory factors in the gum and hippocampus.NAC can effectively reduce the alveolar bone absorption of AD mice caused by periodontitis,reduce the level of inflammatory factors in the gingiva and hippocampus,and reduce the damage of nerve cells in the hippocampus.