米麴菌與北蟲草菌發酵萃取物對肺炎黴漿菌之影響

The effect of Aspergillus oryzae and Cordyceps militaris fermentation extract on Mycoplasma pneumoniae

李蕙伃(Hui-Yu Lee)

指導教授 ： 陳俊任

國立臺灣大學/生命科學院/生化科技學系/碩士(2022年)

https://doi.org/10.6342/NTU202200394

摘要

肺炎黴漿菌（Mycoplasma pneumoniae）為社區型肺炎（community-acquired pneumonia）常見的致病菌之一，其致病機制為透過感染並破壞呼吸道上皮細胞，使宿主容易受到其他病菌的二次感染，此外，肺炎黴漿菌也會刺激肺泡巨噬細胞（alveolar macrophage）引起發炎反應而造成肺部組織的受損。在本研究中，會探討米麴菌（Aspergillus oryzae）以及北蟲草菌（Cordyceps militaris）的發酵萃取物是否能夠減緩肺炎黴漿菌所引起的發炎反應，以及抑制肺炎黴漿菌生長與對上皮細胞的感染能力。研究結果顯示，在細胞實驗中，米麴菌的發酵萃取物能夠降低肺泡巨噬細胞在受到肺炎黴漿菌刺激後所產生的TNF-α和IL-6，此外，米麴菌的發酵萃取物亦能抑制肺炎黴漿菌的生長以及對上皮細胞的感染能力，然而在北蟲草菌的發酵萃取物中則無法看到上述的效果。而在感染肺炎黴漿菌以引起肺部發炎反應的動物模型中，以口服的方式給予米麴菌發酵萃取物能夠減少嗜中性白血球以及單核球浸潤至肺部，且在支氣管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中也測得較低的TNF-α、IL-6、IL-1β、KC以及MCP-1的含量，而在給予北蟲草菌的發酵萃取物的結果中則沒有影響。綜上所述，顯示米麴菌發酵萃取物能夠成為預防黴漿菌肺炎的潛在藥物。

關鍵字

肺炎黴漿菌 ； 米麴菌 ； 北蟲草菌 ； 肺炎 ； 肺泡巨噬細胞 ； 肺上皮細胞

並列摘要

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. The pathogenic mechanism of M. pneumoniae is to infect and destruct respiratory epithelial cells, making the host susceptible to secondary infections by other pathogens. In addition, M. pneumoniae stimulates alveolar macrophages to induce inflammatory responses and cause lung damage. In this study, we investigated whether the fermentation extracts of Aspergillus oryzae and Cordyceps militaris could suppress M. pneumoniae-induced inflammatory responses, inhibit Mycoplasma growth and the infectivity in lung epithelial cells. In vitro, the results showed that the Aspergillus oryzae fermentation extract (AOE) suppressed M. pneumoniae-stimulated production of TNF-α and IL-6 in alveolar macrophages. It also inhibited M. pneumoniae growth and its ability to infect epithelial cells. In contrast, the Cordyceps Militaris fermentation extracts (CME) did not show similar effects. In the M. pneumoniae pneumonia mouse model, oral administration of AOE could reduce the infiltration of neutrophils and monocytes into the lungs, as well as lower the levels of TNF-α, IL-6, IL-1β, KC and MCP-1 in the bronchoalveolar lavage fluid. However, CME treatment had no effect on M. pneumoniae pneumonia. Overall, these data indicate that the fermentation extract of Aspergillus oryzae has a potential to be developed as a novel agent for preventing M. pneumoniae pneumonia.

並列關鍵字

Mycoplasma pneumoniae ； Aspergillus oryza ； Cordyceps militaris ； pneumonia ； alveolar macrophage ； lung epithelial cell

參考文獻

1. Waites, K.B. and D.F. Talkington, Mycoplasma pneumoniae and its role as a human pathogen. Clinical Microbiology Reviews, 2004. 17(4): p. 697-728.

2. Wodke, J.A., et al., Dissecting the energy metabolism in Mycoplasma pneumoniae through genome‐scale metabolic modeling. Molecular Systems Biology, 2013. 9(1): p. 653.

3. Seto, S., et al., Involvement of P1 adhesin in gliding motility of Mycoplasma pneumoniae as revealed by the inhibitory effects of antibody under optimized gliding conditions. Journal of Bacteriology, 2005. 187(5): p. 1875-1877.

4. Lind, K., et al., Mycoplasma pneumoniae infection associated with affection of the central nervous system. Acta Medica Scandinavica, 1979. 205(1‐6): p. 325-332.

5. Sands Jr, M.J. and R. Rosenthal, Progressive heart failure and death associated with Mycoplasma pneumoniae pneumonia. Chest, 1982. 81(6): p. 763-765.