- 學位論文
三黃瀉心湯及其代謝物與苯唑西林對抗藥性金黃葡萄球菌抑菌作用的評估
Evaluation of the Antimicrobial Effects by Herbal Medicine-San-Huang-Sie-Sin-Tang and its Metabolites with Oxacillin to Methicillin-resistant Staphylococcus aureus
摘要
細菌感染的問題是醫界存在已久的問題，而對甲氧苯青黴素具抗藥性的金黃色葡萄球菌，是目前最受國際間注意的多重抗藥性菌株，為了防止抗藥性致病原的增加與擴散，抗生素的使用就應更加小心謹慎；中藥是我國先民歷經千百年智慧與經驗累積的結晶，其中不少是具有抗菌作用的，例如黃連、黃芩、大黃等。近年來，性能相近的中西藥合併治療日趨廣泛，其效果也愈來愈受到國內外學者的重視。本研究即針對中藥複方三黃瀉心湯及其代謝物與西藥抗生素苯唑西林彼此產生協同作用後，是否可降低對抗藥性的金黃色葡萄球菌菌株之最低抑菌濃度進行探討。 本實驗先將三黃瀉心湯科學中藥配製成中藥紙錠對金黃色葡萄球菌、綠膿桿菌、大腸桿菌、克雷白氏菌、不動桿菌、腸道桿菌屬、沙門氏桿菌、痢疾桿菌、產氣單胞菌、念珠菌、抗藥性大腸桿菌、抗藥性克雷白氏菌、抗藥性不動桿菌、抗藥性腸球菌等菌株進行篩選；再將三黃瀉心湯及其組成成份大黃、黃連、黃芩之科學中藥稀釋成1-32 mg/ml範圍之濃度，再前四者的代謝物稀釋10倍、20倍、40倍及100倍，利用肉湯稀釋敏感度分析的方法，測試三黃瀉心湯科學中藥及其代謝物的最低抑菌濃度；最後選擇三黃瀉心湯科學中藥沒有殺菌效果的最低濃度，濃度範圍為（0.5-16 mg/ml）及濃度範圍為（1-64μg/ml）之2倍連續稀釋的苯唑西林，及稀釋10倍後之三黃瀉心湯代謝物和濃度範圍為（1-128μg/ml）之2倍連續稀釋的苯唑西林，利用肉湯稀釋敏感度分析的方法測試彼此的協同情況。研究結果顯示三黃瀉心湯對金黃色葡萄球菌抑菌效果最好，三黃瀉心湯科學中藥在16 mg/ml 時對抗藥性的金黃色葡萄球菌會產生抑菌效果，其代謝物在稀釋10倍時沒有抑菌效果；在中西藥協同作用方面，8 mg/ml的三黃瀉心湯科學中藥與苯唑西林合併使用時可降低苯唑西林的使用劑量由原16μg/ml降為8μg/ml；其代謝物稀釋10倍時無法降低苯唑西林的使用劑量。但代謝物是可以被人體直接吸收的，所以代謝物的測試結果對臨床治療上具有絕對參考的價值，值得爾後深入探討。
並列摘要
In the field of medical science, bacteria infection is a serious problem for decades. Methicillin-resistant Staphylococcus aureus, MRSA, is the worldwide most noted multiple resistant bacteria strain which is resistant to Methicillin. Chinese herbal medicines are the treasures of our ancestors; some of them have the ability of killing bacteria, for example, Rhubarb, Coptis and Scute etc. Recently, the combination therapy of herbal medicine and Western medicine has been taken extensively. Also, there are more and more experts value the outcome of the combination. This study was focused on the killing ability to MRSA. The minimal inhibition concentration（MICs）of SHSST（San – Huang – Sie – Sin - Tang）and its metabolites for inhibited the MRSA（ATCC3300）growth. These medicines were determined by the broth dilution sensitivity analysis method. And the medicines were combined with oxacillin to detect MICs for the MRSA growth. First, SHSST was diluted at 1-32 mg/ml. And the metabolite of SHSST was diluted at 10-fold, 20-fold, 40-fold and 100-fold to detect MICs for bacteria growth. Finally, SHSST was diluted at the concentration of 0.5-16 mg/ml of combined with the concentration of 1-128 μg/ml of oxacillin, which was sequentially diluted in 2-fold serial.Then, the metabolite of SHSST was diluted 10-fold combined with the concentration 1-128 μg/ml of oxacillin, which was sequentially diluted in 2-fold serial. The process was to test the synergistic effect of to inhibit the MRSA growth. The results showed that SHSST could inhibit the growth of MRSA at the concentration of 16 mg/ml. Its metabolite was still unable to inhibit the growth of MRSA even at only 10-fold dilution. With the combination of 8mg/ml SHSST, the dosage of oxacillin could be reduced from 16μg/ml to 8μg/ml for the inhibition of the growth of MRSA. Howeveer, 10-fold dilution of the metabolite was still unable to reduce the oxacillin's MICs for the inhibition of the growth of MRSA. Although the result of metabolite was unacceptable; it could be directly taken by human body. The result of metabolite could be a reference for clinical diagnosis. It is worthy for further investigation.