阿黴素是治療癌患者的重要化療藥物，然而阿黴素化療常引起心臟以及腸道發炎等不良副作用。由於腸道微生物群對於免疫系統的健康運作至關重要，而且腸道微生物群產生的代謝物質可以通過腸心軸(Gut-Heart Axis)影響心臟的功能。恢復腸道微生物群的方法之一就是使用合生元，而合生元是將益生菌與益生質結合使用。為探討合生元是否可以有效緩解阿黴素化療常引起的心臟與腸道發炎，本研究選用阿黴素化療的小鼠，並且給予口服合生元處理，藉此探討合生元是否可以有效緩解阿黴素化療引起的心臟與腸道發炎。本研究利用組織化學染色觀察結果顯示阿黴素化療的小鼠會有心肌發炎與腸道發炎的情形發生，而利用免疫組織化學染色觀察，結果發現，化療可以誘導與小鼠心臟和腸道組織中細胞凋亡相關的氧化壓力、發炎和蛋白質表現有顯著增加。而給予口服合生元處理的化療小鼠，不但心肌發炎與腸道發炎的情形明顯減緩，而且小鼠小鼠心臟和腸道組織中細胞凋亡相關的氧化壓力、發炎和蛋白質表現有顯著減少許多。綜合上述研究結果，我們認為適時給予阿黴素化療的癌患者合生元處理，應該可以大大保護化療藥物引起心臟以及腸道發炎的不良副作用。

Doxorubicin is an important chemotherapy drug for the treatment of cancer patients. However, doxorubicin chemotherapy often causes adverse side effects such as heart and intestinal inflammation. Because the intestinal microbiota is crucial to the healthy of the immune system, and the metabolic substances produced by the intestinal microbiota can affect the heart function through the gut-heart axis. One way to restore gut microbiome is through the use of synbiotics, which combine probiotics with prebiotics. In order to explore whether synbiotics can effectively alleviate heart and intestinal inflammation caused by doxorubicin chemotherapy, this study selected ICR mice treated with doxorubicin chemotherapy, and gave oral synbiotics to explore whether synbiotics can effectively alleviate doxorubicin-induced inflammation. This study used histochemical staining to observe that mice treated with doxorubicin chemotherapy should have myocardial and intestinal inflammation. Immunohistochemical staining was used to observe that chemotherapy can increase protein expressions of oxidative stress, inflammation, and apoptosis in the myocardium and intestinal tissue of mice. Those chemotherapy mice treated with oral synbiotics not only significantly reduce myocardial and intestinal inflammation, but also significantly reduce the protein expression of oxidative stress, inflammation, and apoptosis in the myocardium and intestinal tissue of the mice. Based on our results, we suggested that synbiotic treatment for cancer patients who are given doxorubicin chemotherapy should be able to greatly protect against the adverse side effects of chemotherapy drugs such as heart and intestinal inflammation.

Dorr, R. T., & Von Hoff, D. D. (1994). Cancer Chemotherapy Handbook (2nd Ed.). Appleton & Lange. (n.d.).
Gottesman M. M. (2002). Mechanisms of cancer drug resistance. Annual review of medicine, 53, 615–627.
Jemal, A., Siegel, R., Xu, J., & Ward, E. (2010). Cancer statistics, 2010. CA: a cancer journal for clinicians, 60(5), 277–300.
DeVita, V. T., Lawrence, T. S., & Rosenberg, S. A. (2015). Cancer: Principles & Practice of Oncology (10th Ed.). Wolters Kluwer Health. (n.d.).
Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., & Gianni, L. (2004). Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological reviews, 56(2), 185–229.
Weiss R. B. (1992). The anthracyclines: will we ever find a better doxorubicin?. Seminars in oncology, 19(6), 670–686.
Hortobágyi G. N. (1997). Anthracyclines in the treatment of cancer. An overview. Drugs, 54 Suppl 4, 1–7.
Carvalho, C., Santos, R. X., Cardoso, S., Correia, S., Oliveira, P. J., Santos, M. S., & Moreira, P. I. (2009). Doxorubicin: the good, the bad and the ugly effect. Current medicinal chemistry, 16(25), 3267–3285.
Tacar, O., Sriamornsak, P., & Dass, C. R. (2013). Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. The Journal of pharmacy and pharmacology, 65(2), 157–170.
Octavia, Y., Tocchetti, C. G., Gabrielson, K. L., Janssens, S., Crijns, H. J., & Moens, A. L. (2012). Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. Journal of molecular and cellular cardiology, 52(6), 1213–1225.
Kalyanaraman B. (2020). Teaching the basics of the mechanism of doxorubicin-induced cardiotoxicity: Have we been barking up the wrong tree?. Redox biology, 29, 101394.
Swain, S. M., Whaley, F. S., & Ewer, M. S. (2003). Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer, 97(11), 2869–2879.
Monsuez, J. J., Charniot, J. C., Vignat, N., & Artigou, J. Y. (2010). Cardiac side-effects of cancer chemotherapy. International journal of cardiology, 144(1), 3–15.
Mordente, A., Meucci, E., Silvestrini, A., Martorana, G. E., & Giardina, B. (2009). New developments in anthracycline-induced cardiotoxicity. Current medicinal chemistry, 16(13), 1656–1672.
McGowan, J. V., Chung, R., Maulik, A., Piotrowska, I., Walker, J. M., & Yellon, D. M. (2017). Anthracycline Chemotherapy and Cardiotoxicity. Cardiovascular drugs and therapy, 31(1), 63–75.
Volkova, M., & Russell, R., 3rd (2011). Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Current cardiology reviews, 7(4), 214–220.
Lederman, L., Madden, D., Battle, D., Connolly, H. K., & Smith, M. L. (2016). Patient Advocates Collaborate to Ensure Patients Are Members of Their Own Oncology Care Teams. Journal of oncology practice, 12(11), 980–982.
Shan, K., Lincoff, A. M., & Young, J. B. (1996). Anthracycline-induced cardiotoxicity. Annals of internal medicine, 125(1), 47–58.
Yu, W., & Fang, H. (2007). Clinical trials with oncolytic adenovirus in China. Current
cancer drug targets, 7(2), 141-148.
Myers C. (1998). The role of iron in doxorubicin-induced cardiomyopathy. Seminars in oncology, 25(4 Suppl 10), 10–14.
Yeh, E. T., Tong, A. T., Lenihan, D. J., Yusuf, S. W., Swafford, J., Champion, C., Durand, J. B., Gibbs, H., Zafarmand, A. A., & Ewer, M. S. (2004). Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation, 109(25), 3122–3131.
Cardinale, D., Colombo, A., Lamantia, G., Colombo, N., Civelli, M., De Giacomi, G., Rubino, M., Veglia, F., Fiorentini, C., & Cipolla, C. M. (2010). Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. Journal of the American College of Cardiology, 55(3), 213–220.
Lipshultz, S. E., Alvarez, J. A., & Scully, R. E. (2008). Anthracycline associated cardiotoxicity in survivors of childhood cancer. Heart (British Cardiac Society), 94(4), 525–533.
Takemura, G., & Fujiwara, H. (2007). Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management. Progress in cardiovascular diseases, 49(5), 330–352.
Brana, I., & Tabernero, J. (2010). Cardiotoxicity. Annals of oncology : official journal of the European Society for Medical Oncology, 21 Suppl 7, vii173–vii179.
Olson, R. D., & Mushlin, P. S. (1990). Doxorubicin cardiotoxicity: analysis of prevailing hypotheses. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 4(13), 3076–3086.
Khouri, M. G., Douglas, P. S., Mackey, J. R., Martin, M., Scott, J. M., Scherrer-Crosbie, M., & Jones, L. W. (2012). Cancer therapy-induced cardiac toxicity in early breast cancer: addressing the unresolved issues. Circulation, 126(23), 2749–2763.
Chang, H. M., Moudgil, R., Scarabelli, T., Okwuosa, T. M., & Yeh, E. T. H. (2017). Cardiovascular Complications of Cancer Therapy: Best Practices in Diagnosis, Prevention, and Management: Part 1. Journal of the American College of Cardiology, 70(20), 2536–2551.
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a cancer journal for clinicians, 71(3), 209–249.
Bray, F., Jemal, A., Grey, N., Ferlay, J., & Forman, D. (2012). Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. The Lancet. Oncology, 13(8), 790–801.
Kintzel P. E. (2001). Anticancer drug-induced kidney disorders. Drug safety, 24(1), 19–38.
Miller, K. D., Nogueira, L., Mariotto, A. B., Rowland, J. H., Yabroff, K. R., Alfano, C. M., Jemal, A., Kramer, J. L., & Siegel, R. L. (2019). Cancer treatment and survivorship statistics, 2019. CA: a cancer journal for clinicians, 69(5), 363–385.
Swain, S. M., Whaley, F. S., & Ewer, M. S. (2003). Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer, 97(11), 2869–2879.
Yeh, E. T., & Bickford, C. L. (2009). Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. Journal of the American College of Cardiology, 53(24), 2231–2247.
Rondanelli, M., Faliva, M. A., Perna, S., Giacosa, A., Peroni, G., & Castellazzi, A. M. (2017). Using probiotics in clinical practice: Where are we now? A review of existing meta-analyses. Gut microbes, 8(6), 521–543.
Gianotti, L., Morelli, L., Galbiati, F., Rocchetti, S., Coppola, S., Beneduce, A., Gilardini, C., Zonenschain, D., Nespoli, A., & Braga, M. (2010). A randomized double-blind trial on perioperative administration of probiotics in colorectal cancer patients. World journal of gastroenterology, 16(2), 167–175.
Demers, M. S., Pal, S., & Delp, S. L. (2014). Changes in tibiofemoral forces due to variations in muscle activity during walking. Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 32(6), 769–776.
Consoli, D., Marin, G., Marzucchi, A., & Vona, F. (2016). Do green jobs differ from non-green jobs in terms of skills and human capital?. Research Policy, 45(5), 1046-1060.
Karmazyn, M., & Gan, X. T. (2023). Probiotics as potential treatments to reduce myocardial remodelling and heart failure via the gut-heart axis: state-of-the-art review. Molecular and Cellular Biochemistry, 478(11), 2539-2551.
Gómez-Guzmán, M., Toral, M., Romero, M., Jiménez, R., Galindo, P., Sánchez, M., Zarzuelo, M. J., Olivares, M., Gálvez, J., & Duarte, J. (2015). Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats. Molecular nutrition & food research, 59(11), 2326–2336.
Chi, X., Yan, R., Zhang, J., Zhang, G., Zhang, Y., Hao, M., Zhang, Z., Fan, P., Dong, Y., Yang, Y., Chen, Z., Guo, Y., Zhang, J., Li, Y., Song, X., Chen, Y., Xia, L., Fu, L., Hou, L., Xu, J., … Chen, W. (2020). A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science (New York, N.Y.), 369(6504), 650–655.
Tang, K. L., Pierce, M. P., & Guénard, B. (2019). Review of the genus Strumigenys (Hymenoptera, Formicidae, Myrmicinae) in Hong Kong with the description of three new species and the addition of five native and four introduced species records. ZooKeys, 831, 1.
Theodoropoulos, G. E., Memos, N. A., Peitsidou, K., Karantanos, T., Spyropoulos, B. G., & Zografos, G. (2016). Synbiotics and gastrointestinal function-related quality of life after elective colorectal cancer resection. Annals of gastroenterology, 29(1), 56–62.