牙周炎加重主动脉弓缩窄诱导的小鼠心肌肥厚

doi:10.3969/j.issn.1674-8115.2022.09.014

上海交通大学学报（医学版） ›› 2022, Vol. 42 ›› Issue (9): 1275-1287.doi: 10.3969/j.issn.1674-8115.2022.09.014

牙周炎加重主动脉弓缩窄诱导的小鼠心肌肥厚

李露(), 李雨霖(), 柳燕, 段胜仲()

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，国家口腔疾病临床医学研究中心，上海市口腔医学重点实验室，上海 200125

收稿日期:2022-05-18 接受日期:2022-08-06 出版日期:2022-09-28 发布日期:2022-09-28
通讯作者: 段胜仲 E-mail:lilu123@sjtu.edu.com;duansz@shsmu.edu.cn
作者简介:李　露（1997—），女，硕士生；电子信箱：lilu123@sjtu.edu.com
李雨霖（1995—），男，博士生；电子信箱：liyulin597926717@sjtu.edu.cn第一联系人：（李露和李雨霖为本文共同第一作者）
基金资助:
国家自然科学基金(81725003);上海市高水平地方高校创新团队(SHSMU-ZDCX20212500)

Periodontitis aggravates transverse aortic constriction-induced cardiac hypertrophy in mice

LI Lu(), LI Yulin(), LIU Yan, DUAN Shengzhong()

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 200125, China

Received:2022-05-18 Accepted:2022-08-06 Online:2022-09-28 Published:2022-09-28
Contact: DUAN Shengzhong E-mail:lilu123@sjtu.edu.com;duansz@shsmu.edu.cn
Supported by:
National Natural Science Foundation of China(81725003);Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20212500)

摘要/Abstract

摘要：

目的·研究牙周炎（periodontitis，PD）对主动脉弓缩窄（transverse aortic constriction，TAC）诱导的小鼠心肌肥厚的作用和机制。方法·将25只 C57BL/6J小鼠随机分为假手术（Sham）组、TAC组及TAC+PD组。用丝线结扎加涂抹龈下菌斑的方法诱导PD模型，并在PD模型建立后做TAC手术。在假手术或TAC手术后4周，用心脏超声评估心脏功能，然后处死小鼠并取材，其样本用于实时定量聚合酶链式反应（qRT-PCR）、免疫组织化学检测、免疫荧光检测、16S rRNA基因测序。结果·TAC+PD组小鼠的牙槽骨吸收和牙龈组织炎症相关基因的表达均高于Sham组和TAC组，表明在TAC小鼠中成功建立了PD模型。与TAC组相比，TAC+PD组小鼠的左心室射血分数（EF）、左心室缩短分数（FS）值都显著降低，表明PD加重TAC导致的心功能受损。与TAC组相比，TAC+PD组小鼠的心脏质量/体质量比率（HW/BW）和心脏质量/胫骨长度比率（HW/TL）升高、肺质量/体质量比率（LW/BW）升高、心肌细胞横截面积增大、心肌肥厚相关的基因表达水平也显著升高，表明PD加重TAC诱导的心肌肥厚和心力衰竭。与TAC组相比，TAC+PD组小鼠的心肌纤维化程度上升、纤维化相关基因上调、脾脏胫骨长度比率（SW/TL）上升、炎症相关基因上调，表明PD加重了TAC诱导心肌细胞的纤维化和炎症反应。16S rRNA基因测序结果表明，TAC+PD组小鼠的口腔结扎丝线中链球菌属（Streptococcus）和韦荣球菌属（Veillonella）的相对丰度显著高于TAC组；TAC+PD组小鼠的心脏中罗尔斯通菌属（Ralstonia）和嗜糖假单胞菌属（Pelomonas）的相对丰度显著高于TAC组；而且TAC+PD组小鼠的心脏中罗尔斯通菌属和嗜糖假单胞菌属的相对丰度显著高于其口腔结扎丝线。结论·PD能够加重TAC术后小鼠心脏功能损害、心肌肥厚和心肌纤维化，并在一定程度上加重心脏的炎症反应，其作用机制可能与罗尔斯通菌属、嗜糖假单胞菌属等口腔微生物相关。

关键词: 牙周炎, 主动脉弓缩窄术, 心肌肥厚, 口腔微生物

Abstract:

Objective ·To study the effects of periodontitis (PD) on transverse aortic constriction (TAC)-induced cardiac hypertrophy in mice and explore the mechanisms. Methods ·Twenty-five C57BL/6J mice were randomly divided into Sham operation (Sham) group, transverse aortic constriction (TAC) group, and periodontitis combined with TAC (TAC+PD) group. PD was induced by ligation of mouse molars and application of subgingival plaques of PD patients. TAC surgery was performed after the establishment of PD model. Cardiac function was assessed by echocardiography at 4 weeks after Sham or TAC surgery. The mice were then sacrificed and the samples were collected for quantitative realtime PCR (qRT-PCR), immunohistochemistry, immunofluorescence, and 16S rRNA gene sequencing. Results ·The mice in the TAC+PD group manifested significantly more resorption of the alveolar bone and higher expression of inflammatory genes in gingiva compared to Sham and TAC groups, demonstrating successful establishment of PD models in TAC mice. Compared to those in the TAC group, the mice in the TAC+PD group had significantly lower left ventricular ejection fraction (EF) and left ventricular shortening fraction (FS), illustrating that PD exacerbated TAC-induced cardiac dysfunction. Compared to those in the TAC group, the mice in the TAC+PD group had significantly bigger heart weight to body weight ratio (HW/BW) and heart weight to tibia length ratio (HW/TL), lung weight to body weight ratio (LW/BW), and cross-sectional area of cardiomyocytes, as well as higher expression of hypertrophy-related genes, demonstrating that PD exacerbated TAC-induced cardiac hypertrophy and heart failure. Compared to those in the TAC group, the mice in the TAC+PD group had significantly larger fibrotic areas and higher expression of fibrosis-related genes in the heart, bigger spleen weight to tibia length ratio (SW/TL) and higher expression of inflammatory genes in the heart, illustrating that PD exacerbated TAC-induced cardiac fibrosis and inflammation. Results of 16S rRNA gene sequencing showed that relative abundances of Streptococcus and Veillonella were significantly increased in the oral ligatures of mice in the TAC+PD group compared to the TAC group. Relative abundances of Ralstonia, and Pelomonas were significantly increased in the hearts of mice in the TAC+PD group. Comparison of oral microbiota and heart microbiota of the mice in the TAC+PD group revealed that relative abundances of Ralstonia and Pelomonas in hearts were significantly higher than those in oral ligatures. Conclusion ·PD aggravates TAC-induced cardiac dysfunction, cardiac hypertrophy, fibrosis, and inflammation in mice. The mechanisms may be related to alterations in oral microbiota, particularly bacterial genera including Ralstonia and Pelomonas.

Key words: periodontitis (PD), transverse aortic constriction (TAC), cardiac hypertrophy, oral microbiota

中图分类号:

R365

李露, 李雨霖, 柳燕, 段胜仲. 牙周炎加重主动脉弓缩窄诱导的小鼠心肌肥厚[J]. 上海交通大学学报（医学版）, 2022, 42(9): 1275-1287.

LI Lu, LI Yulin, LIU Yan, DUAN Shengzhong. Periodontitis aggravates transverse aortic constriction-induced cardiac hypertrophy in mice[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(9): 1275-1287.

图/表 9

表1 qRT-PCR所用的引物序列（5′→3′）

Tab 1 A list of the primers used in the qRT-PCR （5′→3′）

Gene	Forward primer	Reverse primer
Il-1β	GAAATGCCACCTTTTGACAGTG	TGGATGCTCTCATCAGGACAG
Il-17a	TTTAACTCCCTTGGCGCAAAA	CTTTCCCTCCGCATTGACAC
Il-6	CTGCAAGAGACTTCCATCCAG	AGTGGTATAGACAGGTCTGTTGG
Il-18	GACTCTTGCGTCAACTTCAAGG	CAGGCTGTCTTTTGTCAACGA
Ifn-γ	ATGAACGCTACACACTGCATC	CCATCCTTTTGCCAGTTCCTC
Ctgf	GGGCCTCTTCTGCGATTTC	ATCCAGGCAAGTGCATTGGTA
Col1a1	CTGGCGGTTCAGGTCCAAT	TTCCAGGCAATCCACGAGC
Col3a1	CTGTAACATGGAAACTGGGGAAA	CCATAGCTGAACTGAAAACCACC
Acta1	CCCAAAGCTAACCGGGAGAAG	CCAGAATCCAACACGATGCC
Nppa	GCTTCCAGGCCATATTGGAG	GGGGGCATGACCTCATCTT
β-Mhc	CGGACCTTGGAAGACCAGAT	GACAGCTCCCCATTCTCTGT
Gapdh	AGGTCGGTGTGAACGGATTTG	TGTAGACCATGTAGTTGAGGTCA
β-actin	GGCTGTATTCCCCTCCATCG	CCAGTTGGTAACAATGCCATGT

图1 TAC结合PD小鼠的牙周炎表型特征Note： A. Graphical illustration of experimental design. w—week. B/C. Representative methylene blue staining of mouse maxillae illustrating CEJ-ABC distance (B) and space between CEJ and ABC (C). D/E. Quantification of CEJ-ABC distance (D) and area between CEJ and ABC (E). F. qRT-PCR analysis of inflammatory genes in mouse gingiva.

Fig 1 Phenotypical characterization of periodontitis in mice with or without TAC

图2 PD加重TAC诱导的小鼠心脏功能障碍Note： A. Representative echocardiographic images of mice 4 weeks after sham or TAC operations. B. Quantification of left ventricle ejection fraction (EF) and left ventricle fractional shortening (FS) based on echocardiography.

Fig 2 PD exacerbating TAC-induced cardiac dysfunction in mice

图3 PD加重TAC诱导的小鼠心肌肥厚Note： A. Heart weight to body weight ratio (HW/BW) and heart weight to tibia length ratio (HW/TL). B. Lung weight to body weight ratio (LW/BW). C/D. Representative images of H-E staining (C) and WGA staining (D) of cardiac cross-sections 4 weeks after sham or TAC operations. E. Quantification of cardiomyocyte size based on WGA staining. F. qRT-PCR analysis of hypertrophy-related genes in left ventricles 4 weeks after sham or TAC operations.

Fig 3 PD exacerbating TAC-induced cardiac hypertrophy in mice

图4 PD加重TAC诱导的小鼠心肌纤维化Note： A/B. Representative images of Masson's trichrome staining (A) and sirius red staining (B) of cardiac cross-sections 4 weeks after sham or TAC operations. C. Quantification of myocardial fibrotic area based on sirius red staining. D. qRT-PCR analysis of fibrosis-related genes in left ventricles 4 weeks after sham or TAC operations.

Fig 4 PD aggravating TAC-induced cardiac fibrosis in mice

图5 PD加重TAC诱导的小鼠心脏炎症Note： A. Spleen weight to tibia length ratio (SW/TL) of mice 4 weeks after sham or TAC operations. B?D. qRT-PCR analysis of inflammatory genes Ifn-γ (B), Il-6 (C), and Il-18 (D) in left ventricles 4 weeks after sham or TAC operations.

Fig 5 PD aggravating TAC-induced cardiac inflammation

图6 PD改变TAC小鼠的口腔微生态Note： A. α-diversity of microbiota in oral ligatures assessed by Chao1 and Shannon indices. B. β-diversity of microbiota in oral ligatures analyzed by PCoA based on Bray-Curtis distance. C. Composition of microbiota in oral ligatures showing relative abundances of the 10 most abundant genera. D. Heatmap of relative abundances of the 20 most abundant genera in oral ligatures. E. Taxonomic cladogram of microbiota in oral ligatures using LEfSe (LDA=2). Oral microbiota was analyzed by using 16S rRNA gene sequencing.

Fig 6 PD altering oral microbiota in mice undergoing TAC

图7 PD改变TAC小鼠的心脏微生态Note： A. α-diversity of microbiota in hearts assessed by Chao1 and Shannon indices. B. β-diversity of microbiota in hearts analyzed by PCoA based on Bray-Curtis distance. C. Composition of microbiota in hearts showing relative abundances of the 10 most abundant genera. D. Heatmap of relative abundances of the 20 most abundant genera in hearts. E. Taxonomic cladogram of microbiota in hearts using LEfSe (LDA=2). Heart microbiota was analyzed by using 16S rRNA gene sequencing.

Fig 7 PD altering heart microbiota in mice undergoing TAC

图8 比较TAC结合PD小鼠的口腔微生态与心脏微生态Note： A. Venn diagram showing the overlapped and different genera between oral and heart microbiota. B. Comparison of microbial β-diversity between oral and heart microbiota using PCoA based on Bray-Curtis distance. C. Compositional difference between oral and heart microbiota at phylum level. D. Compositional difference between oral and heart microbiota at genus level. O—oral; H—heart. The numbers (1?5) denote individual mice. E. Taxonomic cladogram presentation of oral and heart microbiota based on LEfSe (LDA=2.72). Microbiota in oral ligatures and hearts was analyzed by using 16S rRNA gene sequencing.

Fig 8 Comparison of oral and heart microbiota in mice with PD undergoing TAC

参考文献 41

1	BROWN L J, OLIVER R C, LÖE H. Periodontal diseases in the US in 1981: prevalence, severity, extent, and role in tooth mortality[J]. J Periodontol, 1989, 60(7): 363-370.
2	KASSEBAUM N J, BERNABÉ E, DAHIYA M, et al. Global burden of severe periodontitis in 1990‒2010: a systematic review and meta-regression[J]. J Dent Res, 2014, 93(11): 1045-1053.
3	SANZ M, MARCO DEL CASTILLO A, JEPSEN S, et al. Periodontitis and cardiovascular diseases: consensus report[J]. J Clin Periodontol, 2020, 47(3): 268-288.
4	HAJISHENGALLIS G, CHAVAKIS T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities[J]. Nat Rev Immunol, 2021, 21(7): 426-440.
5	BOURGEOIS D, INQUIMBERT C, OTTOLENGHI L, et al. Periodontal pathogens as risk factors of cardiovascular diseases, diabetes, rheumatoid arthritis, cancer, and chronic obstructive pulmonary disease: is there cause for consideration? [J]. Microorganisms, 2019, 7(10): 424.
6	HILL J A, OLSON E N. Cardiac plasticity[J]. N Engl J Med, 2008, 358(13): 1370-1380.
7	SHIMIZU I, MINAMINO T. Physiological and pathological cardiac hypertrophy[J]. J Mol Cell Cardiol, 2016, 97: 245-262.
8	NAKAMURA M, SADOSHIMA J. Mechanisms of physiological and pathological cardiac hypertrophy[J]. Nat Rev Cardiol, 2018, 15(7): 387-407.
9	BAI L, CHEN B Y, LIU Y, et al. A mouse periodontitis model with humanized oral bacterial community[J]. Front Cell Infect Microbiol, 2022, 12: 842845.
10	WEI X, WU B, ZHAO J, et al. Myocardial hypertrophic preconditioning attenuates cardiomyocyte hypertrophy and slows progression to heart failure through upregulation of S100A8/A9[J]. Circulation, 2015, 131(17): 1506-1517;discussion1517.
11	ZAURA E, KEIJSER B J F, HUSE S M, et al. Defining the healthy “core microbiome” of oral microbial communities[J]. BMC Microbiol, 2009, 9: 259.
12	SEGATA N, IZARD J, WALDRON L, et al. Metagenomic biomarker discovery and explanation[J]. Genome Biol, 2011, 12(6): R60.
13	KOREN O, SPOR A, FELIN J, et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis[J]. Proc Natl Acad Sci U S A, 2011, 108(Suppl 1): 4592-4598.
14	KINANE D F, STATHOPOULOU P G, PAPAPANOU P N. Periodontal diseases[J]. Nat Rev Dis Primers, 2017, 3: 17038.
15	ARMINGOHAR Z, JØRGENSEN J J, KRISTOFFERSEN A K, et al. Bacteria and bacterial DNA in atherosclerotic plaque and aneurysmal wall biopsies from patients with and without periodontitis[J]. J Oral Microbiol, 2014, 6. DOI: 10.3402/jom.v6.23408.eCollection 2014.
16	MAHENDRA J, MAHENDRA L, FELIX J, et al. Prevelance of periodontopathogenic bacteria in subgingival biofilm and atherosclerotic plaques of patients undergoing coronary revascularization surgery[J]. J Indian Soc Periodontol, 2013, 17(6): 719-724.
17	SHI B C, LUX R, KLOKKEVOLD P, et al. The subgingival microbiome associated with periodontitis in type 2 diabetes mellitus[J]. ISME J, 2020, 14(2): 519-530.
18	LIU X H, TIAN K, MA X R, et al. Analysis of subgingival microbiome of periodontal disease and rheumatoid arthritis in Chinese: a case-control study[J]. Saudi J Biol Sci, 2020, 27(7): 1835-1842.
19	KNÖLL R, IACCARINO G, TARONE G, et al. Towards a re-definition of 'cardiac hypertrophy' through a rational characterization of left ventricular phenotypes: a position paper of the Working Group 'Myocardial Function' of the ESC[J]. Eur J Heart Fail, 2011, 13(8): 811-819.
20	MCLELLAN A J A, ELLIMS A H, PRABHU S, et al. Diffuse ventricular fibrosis on cardiac magnetic resonance imaging associates with ventricular tachycardia in patients with hypertrophic cardiomyopathy[J]. J Cardiovasc Electrophysiol, 2016, 27(5): 571-580.
21	ALMAAS V M, HAUGAA K H, STRØM E H, et al. Increased amount of interstitial fibrosis predicts ventricular arrhythmias, and is associated with reduced myocardial septal function in patients with obstructive hypertrophic cardiomyopathy[J]. Europace, 2013, 15(9): 1319-1327.
22	MANN D L. Innate immunity and the failing heart: the cytokine hypothesis revisited[J]. Circ Res, 2015, 116(7): 1254-1268.
23	TRACHTENBERG B H, HARE J M. Inflammatory cardiomyopathic syndromes[J]. Circ Res, 2017, 121(7): 803-818.
24	HEUSCH G, LIBBY P, GERSH B, et al. Cardiovascular remodelling in coronary artery disease and heart failure[J]. Lancet, 2014, 383(9932): 1933-1943.
25	WEI Y P, SHI M, ZHEN M, et al. Comparison of subgingival and buccal mucosa microbiome in chronic and aggressive periodontitis: a pilot study[J]. Front Cell Infect Microbiol, 2019, 9: 53.
26	JI S, KIM Y, MIN B M, et al. Innate immune responses of gingival epithelial cells to nonperiodontopathic and periodontopathic bacteria[J]. J Periodontal Res, 2007, 42(6): 503-510.
27	PINHO-GOMES A C, NASIR A, MOSCA R, et al. Intraoperative diagnosis of mitral valve endocarditis secondary to Paenibacillus provencensis[J]. Ann R Coll Surg Engl, 2017, 99(2): e54-e55.
28	ZIGANSHINA E E, SHARIFULLINA D M, LOZHKIN A P, et al. Bacterial communities associated with atherosclerotic plaques from Russian individuals with atherosclerosis[J]. PLoS One, 2016, 11(10): e0164836.
29	SCHÄFFLER H, HERLEMANN D P R, ALBERTS C, et al. Mucosa-attached bacterial community in Crohn′s disease coheres with the clinical disease activity index[J]. Environ Microbiol Rep, 2016, 8(5): 614-621.
30	WANG Z N, HAZEN J, JIA X, et al. The nutritional supplement L-alpha glycerylphosphorylcholine promotes atherosclerosis[J]. Int J Mol Sci, 2021, 22(24): 13477.
31	TOYA T, CORBAN M T, MARRIETTA E, et al. Coronary artery disease is associated with an altered gut microbiome composition[J]. PLoS One, 2020, 15(1): e0227147.
32	LI Z H, WU Z Y, YAN J Y, et al. Gut microbe-derived metabolite trimethylamine N-oxide induces cardiac hypertrophy and fibrosis[J]. Lab Invest, 2019, 99(3): 346-357.
33	ZHAO M M, WEI H R, LI C Z, et al. Gut microbiota production of trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy[J]. Nat Commun, 2022, 13(1): 1757.
34	HEINEKE J, MOLKENTIN J D. Regulation of cardiac hypertrophy by intracellular signalling pathways[J]. Nat Rev Mol Cell Biol, 2006, 7(8): 589-600.
35	BILLET S, BARDIN S, VERP S, et al. Gain-of-function mutant of angiotensin Ⅱ receptor, type 1A, causes hypertension and cardiovascular fibrosis in mice[J]. J Clin Invest, 2007, 117(7): 1914-1925.
36	BOUTHIER J D, DE LUCA N, SAFAR M E, et al. Cardiac hypertrophy and arterial distensibility in essential hypertension[J]. Am Heart J, 1985, 109(6): 1345-1352.
37	SRIVASTAVA P M, CALAFIORE P, MACISAAC R J, et al. Prevalence and predictors of cardiac hypertrophy and dysfunction in patients with type 2 diabetes[J]. Clin Sci (Lond), 2008, 114(4): 313-320.
38	HU Q X, ZHANG H L, GUTIÉRREZ CORTÉS N, et al. Increased Drp1 acetylation by lipid overload induces cardiomyocyte death and heart dysfunction[J]. Circ Res, 2020, 126(4): 456-470.
39	RUBIN S A, FISHBEIN M C, SWAN H J. Compensatory hypertrophy in the heart after myocardial infarction in the rat[J]. J Am Coll Cardiol, 1983, 1(6): 1435-1441.
40	PFEFFER M A, BRAUNWALD E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications[J]. Circulation, 1990, 81(4): 1161-1172.
41	EVERETT R J, TASTET L, CLAVEL M A, et al. Progression of hypertrophy and myocardial fibrosis in aortic stenosis: a multicenter cardiac magnetic resonance study[J]. Circ Cardiovasc Imaging, 2018, 11(6): e007451.

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牙周炎加重主动脉弓缩窄诱导的小鼠心肌肥厚

Periodontitis aggravates transverse aortic constriction-induced cardiac hypertrophy in mice

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