臺灣博碩士論文加值系統

牙周炎由細菌引起組織發炎進而破壞，是口腔最常見的慢性發炎疾病，且與許多全身性慢性發炎疾病密切相關。全身性慢性發炎疾病可透過免疫反應和發炎反應影響牙周炎的進展；同時，牙周炎患處的牙周致病菌及發炎物質亦可藉著血流散布至全身組織，進而影響全身性反應。全身性發炎疾病中，糖尿病已被證實和牙周炎相互影響彼此之病理機轉。此外，具唾液腺炎之修格蘭氏症候群患者，其口腔健康亦受到影響。深入了解牙周炎和修格蘭氏症候群或糖尿病相互作用的致病機轉，可以提供更精準的疾病預防與治療，讓牙科醫療達到以病人為中心的全人照護。
本研究的第一個目的為探討格蘭氏症候群患者之牙周狀態，以及原發型修格蘭氏症候群患者唾液分泌的下降與菌相的關係。統合分析的結果顯示修格蘭氏症候群患者與健康者之牙菌斑指數(plaque index，PI)與牙齦指數(gingival index，GI)具有差異。而臨床研究結果則顯示，原發型修格蘭氏症候群患者之非刺激性唾液流速或刺激性唾液流速與臨床口乾指數皆呈負相關，即唾液流速越低、黏膜越乾。以16S核醣體RNA次世代定序分析唾液分泌功能低下者與唾液功能正常者之口腔漱液菌相，發現兩組的菌相各自有群集的現象。
第二個研究目的是探討同時罹患第二型糖尿病與牙周炎的患者在洗牙及深部牙結石刮除(scaling and root planing，SRP)之外，是否應同步給予全身性抗生素(SRP plus antibiotics，SRPa)控制細菌感染，以減少牙周炎和全身性的發炎反應，進而改善糖化血色素數值。我們採用系統性回顧和統合分析進行研究，結果顯示在三個月追蹤時SRP以及SRPa都顯著降低了糖化血色素和牙周囊袋深度。雖然SRPa組相對於SRP組在糖化血色素減少的量並沒有達到統計學上的差異，但能顯著地降低牙周囊袋深度。在術後六個月追蹤時，SRP仍然具有降低糖化血色素和牙周囊袋深度的效果，SRPa只能降低牙周囊袋深度而不能降低糖化血色素。不論是糖化血色素或牙周囊袋深度，SRPa組跟SRP組結果並沒有達到差異性。
因此，我們建議對於修格蘭氏症候群患者需要注意其牙菌斑指數和牙周狀況，加強口腔清潔，並且繼續關注其口內微生物菌相變化。而同時罹患第二型糖尿病及牙周炎的患者需要定期接受口腔檢查及牙周維護治療，因為SRP可以作為第二型糖尿病治療的重要輔助手段，就像飲食控制、運動、口服藥物和胰島素注射一樣。由於SRP 對糖化血色素降低效果在治療6個月下降，因而強烈建議第二型糖尿病合併牙周炎的患者應每三個月接受牙周檢查與維持治療，來協助於這兩種疾病的控制。本研究的主要貢獻，在於證實牙周治療作為全身慢性發炎疾病協同治療的重要性，並建立臨床牙周照護常規應用於全身慢性發炎疾病的臨床照護。

Periodontitis is one of the chronic inflammatory diseases caused by bacteria that destroy tissues, closely associated with many systemic chronic inflammatory diseases. Systemic chronic inflammatory diseases can affect the progression of periodontitis through immune and inflammatory responses; conversely, periodontal pathogens and inflammatory substances at the site of periodontitis can be disseminated throughout the whole body via the blood stream, affecting systemic responses. Among systemic chronic inflammatory diseases, diabetes has been proven to have mutual influence with periodontitis on the pathogenesis of each other. In addition, oral health of individuals with Sjögren's syndrome who suffer from sialadenitis is also affected. A deeper understanding of the pathogenic mechanisms and interaction between periodontitis and Sjögren's syndrome or diabetes can provide more precise disease prevention and treatment, allowing dental care to be patient-centered comprehensive care.
The first purpose of this study was to explore the periodontal status of patients with Sjögren's syndrome, and the association between the reduced salivary flow rate and the microbial composition in patients with primary Sjögren's syndrome. The results of the integrated analysis showed differences in plaque index (PI) and gingival index (GI) between Sjögren's syndrome patients and healthy individuals. Furthermore, a clinical study showed that, in patients with primary Sjögren's syndrome, unstimulated or stimulated saliva flow rate was negatively correlated with clinical dry mouth index, meaning that the lower the salivary flow rate was, the drier the mucous membrane became. Using 16S ribosomal RNA next-generation sequencing, it was shown that the microbial composition in oral mouth rinse obtained from primary Sjögren's syndrome patients with reduced or normal salivary function had distinct clustering patterns.
The second research objective was to investigate that, in addition to scaling and root planing (SRP), whether patients simultaneously suffering from type 2 diabetes and periodontitis should receive systemic antibiotics (SRP plus antibiotics，SRPa) to control bacterial infection, and thus, to reduce periodontitis, systemic inflammatory responses and, as a result, to improve glycated hemoglobin levels. We conducted a systematic review and meta-analysis, and the results showed that at the three-month follow-up, both SRP and SRPa significantly reduced glycated hemoglobin levels and periodontal pocket depth. Compared with the SRP group, there was no statistically significant reduction of glycated hemoglobin levels in the SRPa group. However, SRPa was able to significantly reduce periodontal pocket depth. At the six-month follow-up after the procedures, SRP continued to demonstrate its effectiveness in lowering glycated hemoglobin levels and periodontal pocket depth, while SRPa only reduced periodontal pocket depth and did not significantly affect glycated hemoglobin levels. In terms of both glycated hemoglobin levels and periodontal pocket depth, there were no significant differences between the SRPa group and the SRP group.
Therefore, we recommend that we should pay attention to the plaque index and periodontal condition in patients with Sjögren's syndrome. We need to improve their oral hygiene and continue to monitor changes in their oral microbiota. Patients with type 2 diabetes and periodontitis simultaneously should receive regular oral examinations and periodontal maintenance treatment, since SRP can be an important adjunctive treatment for type 2 diabetes, similar to diet control, exercise, oral medications, and insulin injections. Regarding the effectiveness of SRP in reducing glycated hemoglobin decreases after six months of treatments, it is highly recommended that patients with type 2 diabetes and periodontitis undergo periodontal examinations and maintenance treatment every three months to help control both two diseases. The main contribution of this study was to confirm the importance of periodontal therapy as part of the coordinated treatment of systemic chronic inflammatory diseases and to establish the application of routine clinical periodontal care in the treatment of systemic chronic inflammatory diseases.

中文摘要i
Abstractiii
目錄vi
圖目錄viii
表目錄i
第一章 緒論1
1.1 牙周炎1
1.2 牙周炎與慢性發炎疾病關聯性的相關機轉2
第二章 修格蘭氏症候群患者的牙周狀態4
2.1 文獻回顧4
2.1.1 修格蘭氏症候群流行病學4
2.1.2 修格蘭氏症候群的臨床症狀與診斷4
2.1.3 修格蘭氏症候群患者的唾液6
2.1.4 口腔菌種8
2.1.5 微生物多樣性9
2.1.6 修格蘭氏症候群患者口乾對口腔菌種的影響11
2.1.7 修格蘭氏症候群與牙周炎相關機轉13
2.1.8 統合分析14
2.2 研究目的16
2.2.1 研究目標一：比較修格蘭氏症候群患者與健康者之牙周指數的差異16
(1) 研究方法17
(2) 研究結果20
(3) 討論24
2.2.2 研究目標二：比較修格蘭氏症候群患者的唾液流速、口乾程度以及細菌學分析27
(1) 研究方法28
(2) 研究結果34
(3) 討論36
第三章 牙周炎治療對第二型糖尿病與牙周炎患者血糖控制的影響40
3.1 文獻回顧40
3.1.1 第二型糖尿病的介紹40
3.1.2 第二型糖尿病與牙周炎相關機轉40
3.1.3 牙周治療對血糖控制的效果41
3.2 研究目的43
(1) 研究方法44
(1)-1 納入文章的選擇標準44
(1)-2 文獻搜索策略45
(1)-3 納入文章的質量評估45
(1)-4 數據擷取和整合統計46
(2) 研究結果48
(2)-1 搜尋結果48
(2)-2 納入文章的特性48
(2)-3 質量評估49
(2)-4 資料分析49
(3) 討論54
(3)-1 統合分析結果54
(3)-2 網絡統合分析58
(3)-3 本研究的限制59
(3)-4 對臨床照護的影響與建議60
第四章 綜合討論61
第五章 結論及建議63
第六章 圖65
第七章 表85
第八章 參考文獻116
第九章 附錄：發表著作及引用授權證明125
9.1 發表著作125
9.2 引用授權證明126

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