Periapical lesion following Cnm-positive Streptococcus mutans pulp infection worsens cerebral hemorrhage onset in an SHRSP rat model
Periapical lesion following Cnm-positive Streptococcus mutans pulp infection worsens cerebral hemorrhage onset in an SHRSP rat model
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Cnm 阳性变形链球菌牙髓感染后的根尖周病变加重 SHRSP 大鼠模型中的脑出血发作
DOI：
10.1093/cei/uxac094
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发表时间：
2022
影响因子：
4.6
通讯作者：
Mizuno Noriyoshi
中科院分区：
文献类型：
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作者：
Taniguchi Yuri;Ouhara Kazuhisa;Kitagawa Masae;Akutagawa Keiichi;Kawada-Matsuo Miki;Tamura Tetsuya;Zhai Ruoqi;Hamamoto Yuta;Kajiya Mikihito;Matsuda Shinji;Maruyama Hirofumi;Komatsuzawa Hitoshi;Shiba Hideki;Mizuno Noriyoshi
脑出血严重影响患者的日常生活。变形链球菌及其粘附因子Cnm增加脑出血的不良反应。然而，cnm阳性细菌从根尖病变转移到脑出血部位的机制尚不清楚。因此，我们在高血压大鼠模型中建立了变形链球菌感染的根尖病变，并研究了脑出血相关的神经系统症状。将18只12周龄卒中易感自发性高血压大鼠随机分为未感染组（对照组）、牙部感染变形链球菌KSM153野生型组（Cnm阳性）和KSM153 Δcnm组。免疫荧光染色显示变形链球菌蛋白。测定血清白细胞介素-1β水平。同时还分析了变形链球菌对细胞外基质和人成纤维细胞的粘附情况。抗突变链球菌血清抗体滴度在Cnm阳性和敲除突变体之间具有可比性。然而，感染后3-10天，cnm阳性大鼠的神经症状评分和脑出血评分高于敲除突变体。变形链球菌衍生蛋白的定位是在受损血管附近观察到的。ksm153 WT感染后血清白细胞介素-1β水平显著升高。与cnm阴性的变形链球菌临床分离株相比，cnm阳性的变形链球菌临床分离株对细胞外基质、人牙髓细胞和人脐静脉内皮细胞的粘附能力增强。总之，cnm阳性细菌以细胞外基质为立足点定植于脑尖病变部位，并通过血流影响脑出血。
Cerebral hemorrhage severely affects the daily life of affected individuals. Streptococcus mutans and its adhesion factor Cnm increase the adverse effects of cerebral hemorrhages. However, the mechanism by which Cnm-positive bacteria migrate from apical lesions to cerebral hemorrhage sites is unclear. Therefore, we established an S. mutans-infected apical lesion in a rat model of hypertension and investigated the neurological symptoms associated with cerebral hemorrhage. Eighteen 12-week-old stroke-prone spontaneously hypertensive rats were randomly divided into three groups, ie the no infection (control), dental infection with S. mutans KSM153 wild type (Cnm positive), and KSM153 Δcnm groups. Immunofluorescent staining was performed to visualize S. mutans protein. Serum interleukin-1β levels were measured. The adhesion of S. mutans to the extracellular matrix and human fibroblast cells was also analyzed. Serum antibody titers against S. mutans were comparable between Cnm positive and knockout mutants. However, 3–10 days post-infection, neurological symptom scores and cerebral hemorrhage scores were higher in Cnm-positive rats than in knockout mutants. The localization of S. mutans-derived protein was observed in the vicinity of disrupted blood vessels. Serum interleukin-1β levels significantly increased post-KSM153 WT infection. Cnm-positive S. mutans clinical isolates showed increased adhesion to the extracellular matrix, human dental pulp cells, and human umbilical vein endothelial cells compared with the Cnm-negative S. mutans isolates. In conclusion, Cnm-positive bacteria colonize the apical lesion site using the extracellular matrix as a foothold and affect cerebral hemorrhage via the bloodstream.