由體內細胞激素調節與體外抑菌效能來探討中藥萃取液對牙周病之療效

牙周病是人類最古老也是最普遍的疾病之一，也是導致成年人牙齒脫落的原因之一。牙周病影響牙齒周圍組織，包括牙齦，齒槽骨及牙周韌帶。常見的自覺性症狀有牙齦紅、腫、疼痛、出血及牙齒鬆動等。牙菌斑長久以來即被認為與牙周病的發生有密切關係，牙菌斑控制是預防和治療牙周病的必須措施，因此治療牙周病必須以牙結石括除及抗菌劑來去除牙周致病菌。然而以抗生素來消除牙周致病菌時，其效果常因致病菌的抗藥性不同而有所差異，且長期使用抗生素有可能改變口腔正常菌種的生長，因此抗生素的使用在牙周病的治療上還是有所限制的。 中醫將牙周病歸屬於胃熱的證候，治療的方式以清瀉胃火、補脾益腎為基礎；所以中醫治療牙周病不單只是消炎、止痛、抗菌，更進而提升自身的免疫系統來達到預防的作用。有鑒於此我們選用收載於元朝 李東垣所著蘭室秘藏中的清胃散，來探討傳統中藥治療牙周病的效能與機制。由抑菌研究得知清胃散(500mg/ml)對牙周致病菌Porphyromonas gingivialis、Streptococcus sanguis、Streptococcus mutans有良好的抑菌能力，而分煎清胃散的抑菌能力又優於合煎清胃散；清胃散對牙周致病菌的抑菌能力主要源於其組成生藥：黃連、牡丹皮和升麻。由牙周病病態動物療效研究得知口服清胃散7日後，病態動物牙齦紅、腫、化膿、出血等症狀均得到緩解甚至消除；由病理檢驗發現口服清胃散之病態動物發炎組織呈現縮小的情況，而病態動物服用合煎清胃散比分煎清胃散有較佳療效。由小鼠體內細胞激素檢測發現，牙周病病態動物服用清胃散7日後IL-4呈現上升，IL-2I、FN-γ呈現下降的趨勢，這顯示清胃散對於牙周病病態動物的抗發炎的功效可能與疫功能調節作用有某種程度上的關係。而正常的實驗動物服用清胃散7日後IL-2則呈現上升趨勢亦具有刺激免疫提升作用，這與傳統中醫的補脾說法相契合。健康老鼠在服用合煎清胃散500mg/kg、分煎清胃散500mg/kg 28日後，IFN-γ值呈現下降趨勢這是否與病態動物痊癒有關聯性仍需進一步探討。 我們由清胃散急性及亞急性毒性安全性評估試驗中確認清胃散LD50為每公斤體重大於25公克，無毒性顯示之劑量（NOAEL）應低於25g/kg。且臨床血液生化檢驗數值及對標的器官（target organs:肝、腎）的病理切片檢查也未發現有意義的損傷，因此，清胃散是一具有高度安全性的牙周病治療藥物，值得推廣與應用。

Human beings have been facing diseases at older ages and periodontitis is one of the diseases that affect human. As the name suggested, periodontitis obviously influences the oral cavity in the periodontal region including alveolar bone, cementum, periodontal ligament and gingival. Early symptoms exhibited are withering of teeth, swollen, bleeding and inflamed periodontal. Experiment results demonstrated that the main cause of periodontitis is dental plaque. For this reason, controlling by eradicating or inhibiting the multiplication of dental plaque is believed to be absolute necessary for periodontitis treatment. Medical examinations proved that dental plaque can be successfully removed by employing and applying antibiotics as well as scaling the dental calculus. However, the side effect with administering antibiotic is that it may destroys or affects the normal growth of harmless bacteria. Therefore, the use of antibiotics on periodontitis is limited and not recommended for long-term usage. China medics suggested that the main cause of periodontitis is due to gastric heat. Therefore, cooling the heat and supplementing spleen and invigorating kidney are the first two steps leading to the treatment. The theory supposedly not only relieves pain, reduces inflammation and protects against bacteria but also improves a person’s immune system to barricade against bacteria causing periodontitis. According to the theory, a method found in a Chinese medical book written in Yuan Dynasty named Lan Shi Mi Chang by Li Dong-Huan suggested the use of “QingWeiSan.” The main anti-bacterial agents in QingWeiSan consist of Coptis , Mountan bark and Buybane rhizome. Two types of preparations of QingWeiSan can be made, i.e. soaking the herbs separately and combine the solution together (group A) or soaking the herbs together at the same time (group B). The bactericidal experiment using a concentration of 500mg/mL of QingWeiSan were tested on periodontitis causing bacteria — Porphyromonas gingivialis, Streptococcus sanguis and Streptococcus mutans. The results proved QingWeiSan is effective against the microbes. In bacteriostasis, group A is better than the group B. Furthermore, laboratory animals suffering periodontitis were orally administered two different preparations of QingWeiSan (500mg/mL) for seven days. Significant results were observed with the concentration employed and some sufferers’ inflammation, swell, puss and bleeding were under control and even healed. In comparison of the size of inflammation, group B is better than the group A for healing. In order to examine the immunomodulation effect of QingWeiSan, Cytokine analyses were assayed. Laboratory induced periodontitis mice treated with QingWeiSan for seven days significantly have higher IL-4 concentration and lower IFN-γ in serum. This suggested the effectiveness of QingWeiSan on periodontitis is related with the immune response. Moreover, mock-treated lab mice treated with QingWeiSan (500mg/mL) for seven days increased IL-2 concentration in serum and this matched perfectly with the “supplementing spleen” thesis. Acute toxicity test and Subacute toxicity test of QingWeiSan were also performed in the interest of health and safety for human beings. The results suggested that QingWeiSan is safe and may take into account for future periodontitis’ treatment.