上海九院：牙周炎可恶化小鼠的肝纤维化
- ①在CCl4诱导的小鼠肝纤维化模型中，通过结扎诱导牙周炎（LIP），并移植牙周炎患者的龈下菌斑（PL）；
- ②相比于CCl4组小鼠，LIP+PL+CCl4显著上调血清丙氨酸转氨酶及肝脏羟基脯氨酸的水平，并增加肝纤维化的区域，同时显著升高促纤维化基因的表达及TGF-β的蛋白水平；
- ③牙周炎增加肝纤维化小鼠的免疫细胞（Kupffer细胞、B细胞及Th17细胞）的肝脏累积，上调肝脏炎症基因的表达并激活NF-κB通路；
- ④牙周炎可改变肝纤维化小鼠的口腔及肝脏菌群。
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上海交通大学附属第九人民医院的段胜仲团队与宋忠臣团队在Journal of Clinical Periodontology上发表的一项最新研究，发现在CCl4诱导的肝纤维化小鼠模型中，诱导牙周炎+移植牙周炎患者的口腔菌群，可通过促进炎症并改变肝脏菌群，从而恶化肝功能损伤及肝纤维化。
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The combination of experimental periodontitis and oral microbiota from periodontitis patients aggravates liver fibrosis in mice
牙周炎患者的口腔菌群与实验性牙周炎恶化小鼠的肝纤维化
10.1111/jcpe.13682
2022-06-17, Article
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Aims: Periodontitis (PD) is the sixth most prevalent diseases around the world and is involved in the development and progression of multiple systematic diseases. Previous studies have reported that PD may aggravate liver injuries. The objective of this study was to investigate whether and how PD affected liver fibrosis.
Methods: Ligature-induced PD (LIP) was induced in male C57/B6J mice and subgingival plaques (PL) from patients with PD were applied to mouse teeth. Liver fibrosis was induced by carbon tetrachloride (CCl4) injection. The mice were randomly divided into six groups: Oil, Oil +LIP, Oil +LIP+PL, CCl4, CCl4+LIP, and CCl4+LIP+PL. Alveolar bone resorption was evaluated by methylene blue staining. Hepatic function was analyzed by serum alanine aminotransferase and hepatic hydroxyproline. Picrosirius red and α-SMA staining were used to evaluate fibrotic area. RNA sequencing and quantitative RT-PCR were used to measure gene expression. Western blotting was used to measure protein levels. Flow cytometry was used to analyze accumulation of immune cells. Mouse microbiota was analyzed using 16S rRNA sequencing.
Results: Mice of the CCl4+LIP+PL group displayed higher serum alanine aminotransferase and hepatic hydroxyproline, as well as more Picrosirius red-positive and α-SMA-positive areas in livers than those of the CCl4 group, suggesting that PD (LIP+PL) aggravated CCl4-induced hepatic dysfunction and liver fibrosis. Consistently, expression of fibro-genic genes and protein levels of transforming growth factor β were much higher in the CCl4+LIP+PL group compared to the CCl4 group. Flow cytometry revealed that PD increased the accumulation of immune cells, including Kupffer cells, B cells and Th17 cells, in the liver of mice with CCl4 treatment. PD also increased the expression of inflammatory genes and activated proinflammatory nuclear factor-kappa B pathway in livers of CCl4-injected mice. Moreover, PD altered both oral and liver microbiota in CCl4-injected mice.
Conclusions: PD aggravates CCl4-induced hepatic dysfunction and fibrosis in mice, likely through increase of inflammation and alteration of microbiota in livers.
First Authors:
Lan Bai,Yong-Li Wang,Yan-Lin Chen
Correspondence Authors:
Zhong-Chen Song,Sheng-Zhong Duan
All Authors:
Lan Bai,Yong-Li Wang,Yan-Lin Chen,Hu-Xiao Li,Shi-Wei Zhu,Yan Liu,Zhong-Chen Song,Sheng-Zhong Duan
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