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標題: 以異種移殖動物模式評估小檗鹼微脂體對肝臟腫瘤的影響
Study the Antihepatoma Effect of Liposomal Berberine in a Murine Xenograft Model
作者: 許智傑
Hsu, Chih-Chieh
關鍵字: liposome;微脂體;berberine;huang lian;HepG2 hepatoma cells;nude mice;小檗鹼;黃連;HepG2肝臟腫瘤細胞;裸鼠
出版社: 獸醫學系暨研究所
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微脂體,為一個有磷脂質分子所構成的雙層膜構造,是一個理想的攜帶藥物的物質,可以增加藥物局部到達腫瘤的濃度。微脂體可以減少傳統化療藥物的使用量,延長其循環時間與減少藥物對正常組織的副作用。而小檗鹼,是黃連的主要成分之一,到目前為止,小檗鹼已經被證實有許多藥理學上的作用,特別是含有抗腫瘤的作用。而因為目前擁有較少副作用的抗腫瘤藥是極欲要發展的,因此本實驗主要是利用微脂體將小檗鹼包覆起來後給予,來觀察其對小鼠異種皮下移植人類肝臟腫瘤的影響。實驗中是在每三天一次的治療前將HepG2肝臟腫瘤細胞腹腔注射到裸鼠中。在實驗結束,小鼠犧牲後的血液學與血清生化學檢查結果顯示小檗鹼微脂體及小檗鹼皆沒有發現到明顯的副作用,而傳統化療藥物doxorubicin則會造成發炎反應及肝細胞的受損。並從組織病理學檢查中發現還會導致睪丸的萎縮。另外,實驗結束時,小檗鹼微脂體及小檗鹼的腫瘤重量與腫瘤體積與陰性對照組PBS相比有輕微下降的情形,僅有陽性對照doxorubicin有顯著的抑制作用。免疫組織化學染色結果顯示血管內皮細胞抗原CD31在各個組別間皆沒有顯著差異,但小檗鹼可有效的減少PCNA的細胞增生指數,而小檗鹼微脂體則可以明顯的降低 COX-2的分泌。另外一方面,利用微脂體將小檗鹼包覆起來後給予,確實可以增加小檗鹼在血漿中以及在肝臟、脾臟、腫瘤組織等中的代謝分解速率。然而,因為本實驗的結果僅能證實小檗鹼經微脂體包覆後給予能輕微的抑制腫瘤的生長,未來還需要更多的實驗來研究是否還有其他的因子會影響小檗鹼微脂體的抗腫瘤的作用,以期能改善並加強其抗腫瘤的效果。

Liposomes, a spherical vesicle composed of a phosopholipid bilayer membranes, are ideal drug carriers capable of increasing the local concentration of drug in tumors. Liposomes can reduce the amount of chemotherapeutic agents needed, extend the circulation time within the patient while reduce the side effects to normal tissues. To date, the antitumor effect of berberine, the main component of Coptis chinesnsis, has been proved. Since an antitumor drug with limited side effects is worth developing, my work focuses on assessing the therapeutic effects of liposome encapsulated berberine (liposomal berberine) on human hepatic carcinoma in a murine xenograft model. HepG2 hepatoma cells were injected subcutaneously into nude mice before following a regimented treatment of one dose every three days treatment. The results of hematology and serum biochemistry showed no remarkable side effects caused by liposomal berberine and berberine, whereas traditional chemotherapeutic drug doxorubicin induced both an inflammatory response and hepatocellular injury. Furthermore, there was no abnormal result from the histopathology examination after the liposomal berberine and berberine treatments, whereas testicular atrophy caused by doxorubicin was observed. At the end of this experiment, both the liposomal berberine and berine treatment groups demonstrated slight decrease in both tumor size and mass when compared with the negative control group (PBS). Only the tumor size and mass of the positive control (doxorubicin) differed significantly from the PBS group. Immunohistopathology examination of CD31 was not influenced by the treatments, whereas berberine significantly decreased the CPI of PNCA, while liposomal berberine significantly decreased the secretion of COX-2. Additionally, liposome could delay the elimination rate in plasma and in different tissues. Since the antihepatoma effects of liposomal berberine were insignificant, further studies are needed to investigate the factors which influence the antihepatoma effects of liposomal berberine, in order to enhance its therapeutic effect.
其他識別: U0005-2607201017511000
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