臺灣博碩士論文加值系統

流行病學研究顯示，癌症一直是危害人類生命的一大疾病，尤其是最近幾十年因為飲食習慣及環境污染等因素，使得罹患癌症的比率有年年增高的傾向。肝癌（Hepatocellular carcinoma，HCC）在亞洲是一種非常普遍的癌症，惡性腫瘤已經連續20年位居國人十大死亡原因之首，每年因肝癌死亡的平均人數約有5,000~6,000人，原發性肝癌如未積極治療，病人往往在數個月或數週內死亡，手術切除目前仍是唯一能治癒原發性肝癌的治療方法。桑黃(Phellinus linteus)為眾所皆知寄生於桑樹上的一種橙黃色菇類，在韓國、中國、日本及其他亞洲的國家都被用作為治療腸胃疾病、淋巴疾病與癌症的傳統醫學用藥。桑黃在過去研究中，發現其具有抗腫瘤、抗發炎及免疫調節等之功用。本研究目的為評估桑黃之抗癌能力及其相關免疫機制之探討。本篇研究中動物活體實驗是以八週齡大的SCID/CB-17雄性小白鼠為實驗動物，利用人類肝癌細胞株Hep3B，將誘發小鼠產生腫瘤，再使用灌食的方式口服給予桑黃，劑量由低至高分別為50mg/kg、100mg/kg、200mg/kg，其間並隨時檢測其體重及腫瘤大小等變化。並在餵食八週後，將小鼠犧牲收取血液並取出脾臟細胞作測試。以MTT assay分析脾臟淋巴細胞受刺激後其細胞增生情形；利用流式細胞儀評估脾臟淋巴細胞中T、B淋巴細胞及NK自然殺手細胞增生的數目、自然殺手細胞活性與吞噬細胞活性；接著利用酵素免疫測定法(ELISA)偵測血液中細胞激素IL-12、IFN-γ、TNF-α的變化量。結果顯示，在給予桑黃後，由流式細胞儀結果得知：CD4+與NK自然殺手細胞數目會隨著餵食高劑量與控制組(誘發腫瘤)比較則有顯著的差異存在。另外，由ELISA所測得之細胞激素IL-12、IFN-γ、TNF-α的分泌量上，高劑量與控制組(誘發腫瘤)比較有顯著上升的現象。MTT assay測試中，以Con A給予脾臟淋巴細胞刺激後，發現給予Con A刺激後，高劑量之脾臟淋巴細胞的增生率明顯上升。此外，自然殺手細胞活性與吞噬細胞活性，在餵食高劑量桑黃後，其活性與控制組(誘發腫瘤)比較下，也有顯著上升趨勢。因此由本研究結果推論，長期口服桑黃可能以經由吞噬細胞與NK自然殺手細胞活性增加，進而達到抑制肝癌細胞的生長與抑制癌症的發生。

Epidemiologic study revealed that cancer is still one of the most harmful diseases to human life. The diet intake and the environmental pollution factors augmented the problems in the decades such that the prevalence of cancer trendy to increase year by year. Human hepatocellular carcinoma（HCC） is one of the most common cancers in Asia﹒Malignant disease has been the leading cause of death in Taiwan for twenty years consecutively. There was 5000 to 6000 people died of hepatocellular carcinoma every year. Patients with primary hepatocellular carcinoma will died in few weeks to few months if they can not be treated intensively. At present, surgical resection is still the only modality for cure of the disease. Phellinus linteus, a well-known orange color mushroom and which grows on mulberry trees has been used as a traditional medicine in Korea, China, Japan, and other Asian countries for the treatment of various diseases, including gastroenteric disorders, lymphatic diseases, and various cancers. From previous studies Phellinus linteus has showed to have anti-tumor、anti-inflammatory and immunoregulatory effects. In the present works, the in vivo studies were designed to evaluate the anti-cancer potency and related immune mechanisms of Phellinus linteus. In animal model, the 4 weeks old male SCID/CB-17 mice were bearing with Hep3B cells and divided into 5 groups and oral administered Phellinus linteus at different doseage, 0 mg /Kg bw /day, 50 mg /Kg bw /day, 100 mg /Kg bw /day, and 200 mg /Kg bw /day, respectively for 8 weeks. MTT assay was used for detection of the lymphocyte proliferation rate. The flow cytometry analysis was used to estimate the number of helper T cell, cytotoxic T cell, B cell, and NK cell number, NK cell and phagocyte activity. The ELISA assay was used to determine cytokine (IL-12, IFN-γ, TNF-α) secretion. The result showed that long term oral administration Phellinus linteus in SCID/CB-17 mice bearing with Hep3B cells could increased CD4+ and NK cell numbers, IL-12, IFN-γ and TNF-α secretion rate when compared with control group (induce cancer). The proliferation rate of splenocytes stimulated with Con A was significant increase in MTT assay. In addition, NK cell activity and phagocyte activity were significant increase when compared with control group (cancer induce). Therefore, long term oral administration Phellinus linteus might enhanced the NK cell and phagocyte activity to suppress tumor growth. In conclusion, Phellinus linteus is a anti-tumor potential mushroom.

中文摘要 I
Abstract III
誌謝 V
表目次 VIII
圖目次 IX
第壹章 前言 1
第貳章 文獻回顧 3
第一節 肝臟之簡介 3
第二節 肝癌之介紹 7
第三節 桑黃功能研究 14
第四節 免疫系統與癌症 26
第五節 SCID mice 腫瘤誘發模式（SCID mice xenograft model） 33
第參章 研究動機與目的 35
第肆章 實驗設計 36
第伍章 材料與方法 38
第一節 實驗材料 38
第二節 實驗方法 42
第三節 方法原理介紹 50
第四節 統計分析 52
第陸章 結果 53
第一節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠體重及組織之影響 53
第二節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠腫瘤大小之影響 54
第三節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠存活率之影響 55
第四節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠肝臟組織之影響 56
第五節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠脾臟淋巴細胞增生能力之影響 56
第六節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠脾臟淋巴細胞亞群數目之影響 57
第七節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠血清中細胞激素分泌之影響 59
第八節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠自然殺手細胞活性之影響 60
第九節 餵食不同劑量桑黃對SCID/CB-17植入肝腫瘤細胞小鼠吞噬細胞活性之影響 61
第柒章 討論 78
第捌章 結論 88
參考文獻 91

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