觀察基質金屬蛋白酶-9, 麩胱甘肽過氧化酶及纖溶酶原激活物抑制物-1等發炎調控因子於牙周病及心血管疾病中所扮演的角色

Evaluating the Roles of Inflammatory Mediators, Matrix Metalloproteinase-9(MMP-9), Glutathione Peroxidase(GPx) and Plasminogen Activator Inhibitor-1(PAI-1) between Periodontal Disease and Cardiovascular Disease

王長富(Chaung-Fu Wang)

指導教授 ： 何坤炎 ； 謝耀東

高雄醫學大學/口腔醫學院/牙醫學研究所/碩士(2007年)

https://doi.org/10.6832/KMU.2007.00036

摘要

研究目的：研究證實牙周炎是典型的發炎性疾病，而心血管疾病卻會被發炎性的疾病所產生的發炎因子所影響，在先前研究證實牙周病和心血管疾病確有其相關性，其中一些牙周發炎的因子MMP-9、PAI-1以及GPx在先前的研究中發現對牙周病以及心血管疾病都有其重要的影響，但兩者之間確切的關連性卻尚未被發現，因此本研究的目的在研究在牙周炎的病人及牙周健康的個體間，還有牙周炎的病人在經過牙周治療前後上述三種biomarkers的數值變化，在配合臨床牙周以及心血管疾病的相關指數作對照比較，藉以探討兩者之間的關連性。

研究方法：本研究總共收集10位牙周健康的個體為對照組以及16位牙周炎的病人為實驗組，於實驗前收集實驗組以及對照組的牙齦溝液以及血漿並做牙周病以及心血管疾病的臨床指標資料的收集；之後實驗組在經過牙周病第一期的治療之後，再將所有檢體以及資料收集一次，作為治療前後的比較。以ELISA的實驗方式來測得MMP-9及PAI-1，而GPx的活性則是使用生化活性的kit來檢測。再將三種biomarkers的結果作統計分析比較。

結果：三種biomarkers於實驗組以及對照組中，皆未達統計上顯著差異，實驗組MMP-9的數值在牙齦溝液的總量以及血漿濃度的平均值高於對照組，但未達統計上顯著差異。實驗組於治療後MMP-9在牙齦溝液的濃度(10.46±8.89 vs. 5.41±6.17 ng/dl, p=0.029)、總量(32.52±32.89 vs. 13.94±17.82 ng, p=0.003)以及血漿中濃度(99.56±55.75 vs. 65.82±43.51 ng/dl, p=0.018)中的濃度皆有顯著的降低，臨床牙周指數中的牙齦炎指數和MMP-9的數值改變量有顯著的正相關性；PAI-1於血漿的濃度在治療後數值降低有統計上顯著的傾向(80.99±27.64 vs. 68.71±16.62 ng/dl, p=0.051)，但PAI-1在牙齦溝液的數值則沒有明顯的改變；GPx在治療後牙齦溝液的濃度顯著的上升(7.45±3.13 vs. 11.76±5.63 U/ml)，但於血漿則無顯著差異。在心血管功能檢測方面，頸動脈增厚程度以及ABI數值顯著於實驗組與對照組無顯著的差異，在第一期牙周治療前後兩個數值都沒有明顯的改變。

結論：MMP-9於治療前後牙齦溝液以及血漿的數值皆有顯著的差異，顯示在牙周的治療後確實會降低循環系統中MMP-9的含量，而PAI-1在牙周治療後血漿中的濃度降低，但牙齦溝液中卻沒有明顯的改善；GPx於牙周治療後牙齦溝液的活性顯著的上升，但於血漿中則無顯著差異；在頸動脈增厚程度以及ABI數值的檢測於實驗組及對照組間以及第一期的牙周治療前後皆沒有顯著的改變。代表牙周治療對於三種biomarker皆會造成影響，尤其是MMP-9；但牙周病及心血管疾病的關係則需要更大量的研究來得到更顯著的相關性。

關鍵字

牙齦溝液 ； 牙周病 ； 心血管疾病 ； MMP-9 ； PAI-1 ； GPx

並列摘要

Objectives: Studies have proved that periodontitis is a typical inflammatory disease and cardiovascular disease (CVD) is influenced by inflammatory factors of these diseases. Previous studies have suggested the relationships between CVD and periodontitits. Some inflammatory biomarkers, such as MMP-9, PAI-1 and GPx of periodontitis were found to have important influences both on periodontitis and CVD. The definite relations of these markers between them were not found. As a result, the purpose of this study is to find the difference of these three biomarker between healty controls and patients with periodontitis, and the changes of these biomarkers before and after phase I periodontal therapy. We analyzed clinical periodontal and cardiovascular parameters to understand the relationships between periodontitis and CVD.

Material and Methods: gingival crevicular fluid (GCF) and plasma samples were collected from 10 periodontally healthy controls and 16 periodontitits patients. GCF and plasma samples were colleted again one month after phase I periodontal therapy. Periodontal and cardiovascular parameters were also recorded at the time of sample collection. The MMP-9 and PAI-1 levels were measured with commercial ELISA kits and GPx activity was measured with a commercial biochemical kit.

Results: No significant difference of three markers was found between patients with periodontitis and periodontally healthy controls, but periodontitis group had higher mean total amounts in GCF and concentration in plasma of MMP-9 than healthy controls. However they were not statistically differernt. Significant decreases in the total amounts (32.52±32.89 vs.13.94±17.82 ng, p=0.003), concentration (10.46±8.89 vs. 5.41±6.17 ng/dl, p=0.029) in GCF and concentration in plasma (99.56±55.75 vs. 65.82±43.51 ng/dl, p=0.018) of MMP-9 were found after phase I periodontal therapy. The changes of gingival index and MMP-9 level in GCF had significant positive relationship. The concentration in plasma of PAI-1 had decrease tendency after periodontal therapy (80.99±27.64 vs. 68.71±16.62 ng/dl, p=0.051), but no significant difference was found in GCF levels of PAI-1 after phase I periodontal therapy. Significantly increase in the GPx activity in GCF after phase I periodontal therapy(7.45±3.13 vs. 11.76±5.63 U/ml), but no significant difference was found in plasma. Periodontally healthy and periodontitis groups had no significant difference in the cardiovascular parameters including intima-media wall thickness(IMT) of carotid artery and ankle brachial index(ABI). Both IMT and ABI had no significant change after phase I periodontal therapy.

Conclusion: MMP-9 had significant differences both in GCF and plasma levels before and after periodontal therapy. This shows that MMP-9 levels in circulation decrease after periodontal therapy. PAI-1 had lower concentration in plasma after therapy, but no significant change in GCF was found. GPx activity significantly increased in GCF, but no significant difference was found in plasma. No significant change of ABI and IMT after phase I periodontal therapy. The periodontal therapy had significant influence on three biomarkers, especially MMP-9, but we need more studies to understand more significant relationships between periondotitis and CVD.

並列關鍵字

gingival crevicular fluid ； periodontitis ； cardiovascular disease ； MMP-9 ； PAI-1 ； GPx.

參考文獻

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