Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Int Endod J. 2020 Jun;53(6):812-823. doi: 10.1111/iej.13279. Epub 2020 Mar 9.
First, to determine the feasibility of using the low-density lipoprotein receptor knockout (LDLR KO) mouse model to study apical periodontitis (AP). Secondly, to investigate the causal relationship between AP and atherosclerosis. It was hypothesized that it would be feasible to induce AP and atherosclerosis in LDLR KO mice and find a difference in atherosclerosis between AP and Sham groups.
Using a published methodology, AP was induced in LDLR KO mice by exposing the dental pulp of the four first molars (Tx). Shams received only anaesthesia. Mice were fed a high fat, Western-type diet (WTD), to induce atherosclerosis. At 16 weeks, mice were euthanized and aortas collected to measure atherosclerosis lesion burden (oil red O staining). Periapical lesions were validated using micro-CT and histology. Systemic inflammation was measured using a cytokine array.
Both groups developed a similar degree of atherosclerosis (mean lesion area 7.46 ± 0.44% in the Tx group compared with 7.65 ± 0.46%, in the Sham group, P = 0.77), and a similar degree of inflammation. Periapical lesions (PALs) in all four molars were only identified in a small subset of Tx mice.
A novel mouse model, which combines AP and CVD, was created. This model allows investigation of the relationship between the two diseases, whilst avoiding other potential common confounders. Although no difference in the degree of atherosclerosis was found between the groups, more studies in which the number of periapical lesions, changes in systemic inflammation and the degree of atherosclerosis are correlated are necessary to ultimately determine the impact of AP on CVD.
首先，确定使用低密度脂蛋白受体敲除（LDLR KO）小鼠模型研究根尖周炎（AP）的可行性。其次，探讨 AP 与动脉粥样硬化的因果关系。假设在 LDLR KO 小鼠中诱导 AP 和动脉粥样硬化是可行的，并发现 AP 组和假手术（Sham）组之间在动脉粥样硬化方面存在差异。
使用已发表的方法，通过暴露四颗第一磨牙的牙髓（Tx）在 LDLR KO 小鼠中诱导 AP。Shams 仅接受麻醉。给予高脂西方饮食（WTD）喂养以诱导动脉粥样硬化。16 周后，处死小鼠并收集主动脉以测量动脉粥样硬化病变负担（油红 O 染色）。使用 micro-CT 和组织学验证根尖周病变。使用细胞因子阵列测量全身炎症。
两组均发展出相似程度的动脉粥样硬化（Tx 组的平均病变面积为 7.46±0.44%，而 Sham 组为 7.65±0.46%，P=0.77）和相似程度的炎症。仅在一小部分 Tx 小鼠的四颗磨牙中发现了根尖周病变（PALs）。
创建了一种新的结合 AP 和 CVD 的小鼠模型。该模型允许研究这两种疾病之间的关系，同时避免其他潜在的共同混杂因素。尽管两组之间的动脉粥样硬化程度没有差异，但需要更多研究将根尖周病变数量、全身炎症变化和动脉粥样硬化程度相关联，以最终确定 AP 对 CVD 的影响。
