5-氟尿嘧啶(5FU)是目前廣泛使用的化療藥物之一。然而，由於其通過直接干擾 DNA 合成來殺死癌細胞，因此容易對快速分化的健康黏膜細胞和免疫細胞造成損害。研究證實，益生菌具有抗炎、抗凋亡以及調節體內菌群並提升免疫系統的能力。本實驗室先前的研究發現，補充益生菌可以減輕 5FU 引起的黏膜損傷並改善腸道菌群失衡。最近的研究表明，腸道與口腔微生物群之間存在緊密的相關性。 因此，本實驗旨在探討補充益生菌(Lactobacillus reuteri 合併 Clostridium butyricum, LCs)對 5FU 引起之舌頭損傷、口腔菌群以及腸道免疫功能的影響。在 5FU 誘導前 14 天開始管餵 LCs，並持續至犧牲之日。在第 1 至第 5 天，每天對大鼠進行 50 mg/kg 劑量的 5FU 腹腔注射，並在實驗第 8 天進行犧牲。結果顯示，LCs 補充顯著降低了 5FU 誘導的舌頭發炎細胞激素(IL-6、IL-1!)的產生，顯著提升了舌頭中的 GPx 活性和 GSH 濃度，但僅稍微降低了脂質過氧化物的生成。此外，LCs 補充未能顯著恢復 5FU 所造成的口腔菌群組成及其多樣 性。在免疫功能分析中，LCs 補充顯著改善了部分免疫功能，如脾臟和腸系膜淋巴結(MLN)的部分免疫調控能力以及體液免疫功能(IgM、IgG)。綜合以上實驗結果，益生菌 LCs 顯著緩解了 5FU 引起的舌頭發炎反應並恢復抗氧化能力，但未能顯著調節 5FU 引起的口腔菌群失衡，然而能部分恢復腸道免疫功能。

5-Fluorouracil (5FU) is one of the most widely used chemotherapy drugs. However, due to its mechanism of action that involves directly interfering with DNA synthesis, it can easily cause damage to rapidly differentiating healthy mucosal cells and immune cells. Research has confirmed that probiotics possess anti-inflammatory, anti-apoptotic properties, and the ability to regulate the microbiota and enhance the immune system. Previous studies from our laboratory have shown that probiotic supplementation can alleviate mucosal damage caused by 5FU and improve intestinal microbiota imbalance. Recent studies indicate a close relationship between the microbiota of the gut and the oral cavity. Therefore, this study aims to investigate the effects of probiotics (Lactobacillus reuteri combined with Clostridium butyricum, LCs) supplementation on 5FU-induced tongue damage, oral microbiota, and intestinal immune function. Probiotic administration was initiated 14 days prior to 5FU induction and continued until sacrifice. From days 1 to 5, rats received intraperitoneal injections of 5FU at a dose of 50 mg/kg daily and were sacrificed on day 8 of the experiment. The results showed that LCs supplementation significantly reduced the production of inflammatory cytokines (IL-6 and IL-1β) in the tongue induced by 5FU, significantly increased GPx activity and GSH concentration in the tongue, but only slightly decreased the generation of lipid peroxides. Additionally, LCs supplementation did not significantly restore the composition and diversity of the oral microbiota altered by 5FU. In the analysis of immune function, LCs supplementation significantly improved certain immune functions, such as specific immunoregulatory capabilities of the spleen and mesenteric lymph nodes (MLNs) and humoral immune functions (IgM and IgG). In summary, the experimental results indicate that probiotics LCs significantly alleviated 5FU-induced tongue inflammation and restored antioxidant capacity but did not significantly regulate the oral microbiota imbalance caused by 5FU. However, LCs were able to partially restore intestinal immune function.

摘要 I
Abstract III
縮寫表 V
目次 VIII
表目錄 X
圖目錄 XI
第一章、 緒論 1
第一節、 癌症（惡性腫瘤） 1
第二節、 化療藥物：5-氟尿嘧啶 7
第三節、 免疫細胞組成 18
第四節、 腸道免疫 21
第五節、 口腔微生物 26
第六節、 益生菌 28
第二章、 研究動機 37
第三章、 材料與方法 38
第一節、 藥品與試劑 38
第二節、 抗體 40
第三節、 實驗儀器與耗材 41
第四節、 實驗引子序列 42
第五節、 實驗方法 43
第六節、 統計方法 92
第四章、 結果 93
第一節、 益生菌介入對5FU誘導體位變化之影響 93
第二節、 益生菌介入對5FU誘導舌頭損傷之影響 95
第三節、 益生菌介入對5FU誘導口腔菌相組成之影響 101
第四節、 益生菌介入對5FU誘導腸道免疫改變之影響 107
第五節、 益生菌介入對5FU誘導血液生化數值之影響 112
第六節、 益生菌介入對5FU誘導腸道幹細胞損傷之影響 114
第五章、 討論 116
第六章、 結論 133
第七章、 實驗限制與未來展望 135
第八章、 圖表 136
第九章、 參考文獻 171
第十章、 附錄 195

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