香草乙酮对牙周炎小鼠认知损害的保护作用

doi:10.3969/j.issn.1674-8115.2026.05.005

上海交通大学学报（医学版） ›› 2026, Vol. 46 ›› Issue (5): 594-601.doi: 10.3969/j.issn.1674-8115.2026.05.005

• 论著 · 基础研究 • 上一篇

香草乙酮对牙周炎小鼠认知损害的保护作用

李腾¹^,², 徐丽娜¹^,², 江旖婷¹^,², 何智妍², 宋忠臣¹^,², 周薇²()

^1.上海交通大学医学院附属第九人民医院牙周病科，上海交通大学口腔医学院，国家口腔医学中心，口腔疾病国家临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海 200011
^2.上海交通大学医学院附属第九人民医院口腔微生态与系统性疾病实验室，上海交通大学口腔医学院，国家口腔医学中心，口腔疾病国家临床医学研究中心，上海市口腔医学重点实验室，上海市口腔医学研究所，上海 200125

收稿日期:2025-11-17 接受日期:2026-01-08 出版日期:2026-05-28 发布日期:2026-05-28
通讯作者: 周　薇，研究员，博士；电子信箱：sweetzw@hotmail.com。
基金资助:
国家自然科学基金(82270974);上海交通大学医学院附属第九人民医院交叉基金(JYJC202308)

Protective effect of apocynin on periodontitis-induced cognitive impairment in mice

Li Teng¹^,², Xu Lina¹^,², Jiang Yiting¹^,², He Zhiyan², Song Zhongchen¹^,², Zhou Wei²()

^1.Department of Periodontology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China
^2.Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200125, China

Received:2025-11-17 Accepted:2026-01-08 Online:2026-05-28 Published:2026-05-28
Contact: Zhou Wei, E-mail: sweetzw@hotmail.com.
Supported by:
National Natural Science Foundation of China(82270974);Cross Disciplinary Research Fund of Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine(JYJC202308)

摘要/Abstract

摘要：

目的·探究香草乙酮（apocynin，APO）对牙周炎小鼠认知损害的作用及其机制。方法·选取C57BL/6小鼠，通过龈沟注射牙龈卟啉单胞菌来源脂多糖（Porphyromonas gingivalis lipopolysaccharide，P.g LPS）建立牙周炎模型，并采用腹腔注射香草乙酮对其进行干预。借助显微计算机断层成像（micro computed tomograph，Micro-CT）观察牙槽骨吸收情况；运用旷场实验与莫里斯水迷宫评估小鼠认知功能；采用伊文思蓝染色法检测血脑屏障（blood-brain barrier，BBB）通透性；通过实时荧光定量PCR检测脑组织中紧密连接蛋白闭锁小带蛋白1（zonula occludens-1，Zo-1）、闭合蛋白（occludin，Ocln）以及炎症因子白细胞介素-1β（interleukin-1β，Il-1β）、白细胞介素-8（interleukin-8，Il-8）的mRNA表达水平。结果·与P.g LPS组相比，P.g LPS+APO组小鼠骨体积分数（bone volume/total volume，BV/TV）与骨密度（bone mineral density，BMD）显著提升（P=0.037，P=0.038），骨表面积与骨体积之比（bone surface/bone volume，BS/BV）明显降低（P=0.017）。旷场实验表明，各组活动能力无显著差异。莫里斯水迷宫实验中，在定位航行阶段，自第3日起，P.g LPS+APO组小鼠的潜伏期显著短于P.g LPS组（P<0.001）；在空间探索阶段中，P.g LPS+APO组穿越平台次数明显多于P.g LPS组（P=0.006）。伊文思蓝染色结果显示，P.g LPS+APO组脑组织的吸收度值较P.g LPS组显著降低（P<0.001）。与P.g LPS组相比，P.g LPS+APO组小鼠脑组织中紧密连接蛋白Zo-1（P=0.024）和Ocln（P=0.014）的mRNA表达上调，炎症因子Il-1β和Il-8的mRNA表达下调（P=0.001，P=0.002）。结论·香草乙酮可通过抑制P.g LPS诱导的炎症反应，减轻牙槽骨吸收，降低血脑屏障通透性，进而缓解牙周炎相关认知损害，提示其具有潜在的神经保护作用。

关键词: 香草乙酮, 牙周炎, 认知损害, 血脑屏障

Abstract:

Objective ·To investigate the effect of apocynin (APO) on periodontitis-induced cognitive impairment in mice and its underlying mechanism. Methods ·C57BL/6 mice were used. A periodontitis model was established by injecting Porphyromonas gingivalis lipopolysaccharide (P.g LPS) into the palatal gingival sulcus of the maxillary first molars twice a week for four weeks. Apocynin was administered intraperitoneally as an intervention. Micro-computed tomography (Micro-CT) was used to observe alveolar bone resorption. The open field test and the Morris water maze were employed to assess cognitive function. Evans blue staining was used to detect blood-brain barrier permeability. Real-time qPCR was used to detect the mRNA expression levels of tight junction proteins zonula occludens-1 (Zo-1) and occludin (Occl), as well as interleukin-1β (Il-1β) and interleukin-8 (Il-8) in brains. Results ·Compared with the P.g LPS group, mice in the P.g LPS plus apocynin group showed significantly increased bone volume fraction (BV/TV) and bone mineral density (BMD), and a significantly decreased bone surface/bone volume ratio (BS/BV). In the open field test, there were no significant differences in locomotor activity among the four groups. In the Morris water maze, the latency of the P.g LPS plus apocynin group was significantly shorter than that of the P.g LPS group from day 3 during the navigation phase. In the probe test, the P.g LPS plus apocynin group crossed the target platform significantly more times than the P.g LPS group. Evans blue staining indicated that the absorbance values decreased significantly in the P.g LPS plus apocynin group. Compared with the P.g LPS group, the expression of Zo-1 (P=0.024) and Ocln (P=0.014) was upregulated, while Il-1β (P=0.001) and Il-8 (P=0.002) were downregulated in the brains of mice treated with apocynin. Conclusion ·Apocynin can alleviate periodontitis-induced cognitive impairment by inhibiting P.g LPS-induced inflammation, reducing alveolar bone resorption, and decreasing blood-brain barrier permeability. These findings suggest that apocynin may have potential neuroprotective effects, which provides an experimental basis for the treatment of periodontitis-related cognitive impairment.

Key words: apocynin, periodontitis, cognitive impairment, blood-brain barrier

中图分类号:

R781.4

李腾, 徐丽娜, 江旖婷, 何智妍, 宋忠臣, 周薇. 香草乙酮对牙周炎小鼠认知损害的保护作用[J]. 上海交通大学学报（医学版）, 2026, 46(5): 594-601.

Li Teng, Xu Lina, Jiang Yiting, He Zhiyan, Song Zhongchen, Zhou Wei. Protective effect of apocynin on periodontitis-induced cognitive impairment in mice[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026, 46(5): 594-601.

图/表 8

表1 PCR引物序列（5′→3′）

Tab 1 Primer sequences for PCR （5′→3′）

Gene	Forward sequence	Reverse sequence
Gapdh	ACAGTCCATGCCATCACTGCC	GCCTGCTTCACCACCTTCTTG
Il-1β	AAATCTCGCAGCAGCACATCAA	CCACGGGAAAGACACAGGTAGC
Il-8	CATTAATATTTAACGATGTGGATGCG	GCCTACCATCTTTAAACTGCACAAT
Zo-1	GTTGGCGACCTTGTGGATCT	TAGGAGGCAGGCTTTTGACG
Ocln	CATACCCTTGGTCGCGCTTA	CCAGGCATCCAACAAACTGC

图1 APO对小鼠牙槽骨的影响Note： A. Micro-CT 3D reconstructed images. B. BV/TV. C. BS/BV. D. BMD. ①P=0.021, compared with the Control group; ②P=0.037, compared with the P.g LPS group; ③P=0.009, compared with the Control group; ④P=0.017, compared with the P.g LPS group; ⑤P=0.038, compared with the P.g LPS group.

Fig 1 Effects of apocynin on alveolar bone in mice

图2 APO对小鼠自主活动能力的影响Note： A. Total distance. B. Average speed.

Fig 2 Effects of apocynin on locomotor activity in mice

图3 APO对小鼠空间学习能力的影响Note： Latency to the platform in Morris water maze. ①P=0.003, ②P=0.005, ③P=0.006, the Control group vs the P.g LPS group; ④P<0.001, ⑤P=0.001, ⑥P=0.026, the P.g LPS group vs the P.g LPS+APO group.

Fig 3 Effects of apocynin on spatial learning ability in mice

图4 APO对小鼠空间记忆能力的影响Note： A. Time spent in target quadrants in the Morris water maze. B. Number of platform crossings during the Morris water maze. ①P=0.037, compared with the Control group; ②P=0.008, compared with the P.g LPS group; ③P=0.001, compared with the Control group; ④P=0.006, compared with the P.g LPS group. C. Swimming trajectory.

Fig 4 Effects of APO on spatial memory in mice

图5 APO对小鼠脾脏中炎症因子的mRNA表达水平的影响Note： A. Effects of APO on the relative expression of Il-8. B. Effects of APO on the relative expression of Il-1β. ①P<0.001, compared with the Control group; ②P<0.001, compared with the P.g LPS group; ③P=0.006, compared with the Control group; ④P=0.009, compared with the P.g LPS group.

Fig 5 Effects of APO on the mRNA expression of inflammatory factors in the spleen of mice

图6 APO对小鼠海马中炎症因子mRNA表达水平的影响Note： A. Effects of APO on the relative expression of Il-8. B. Effects of APO on the relative expression of Il-1β. ①P=0.005, compared with the Control group; ②P=0.002, compared with the P.g LPS group; ③P=0.001, compared with the Control group; ④P=0.001, compared with the P.g LPS group.

Fig 6 Effects of APO on the mRNA expression of inflammatory factors in the hippocampus of mice

图7 APO对小鼠BBB通透性和完整性的影响Note： A. Evans Blue content in brain tissue. B. Relative levels of Zo-1 mRNA in the hippocampus. C. Relative levels of Ocln mRNA in the hippocampus.①P<0.001, compared with the Control group; ②P<0.001, compared with the P.g LPS group; ③P=0.025, compared with the Control group; ④P=0.024, compared with the P.g LPS group; ⑤P=0.004, compared with the Control group; ⑥P=0.014, compared with the P.g LPS group.

Fig 7 Effect of APO on the permeability and integrity of the blood-brain barrier in mice

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香草乙酮对牙周炎小鼠认知损害的保护作用

Protective effect of apocynin on periodontitis-induced cognitive impairment in mice

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