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研究生: 洪培菁
Pei-Jing Hung
論文名稱: 以口服3-胺基苯甲醯胺(3-Aminobenzamide)探討由脂多醣體(Lipopolysaccharide)所誘發C57鼠腎病變之發炎反應
The Effects of Oral 3-Aminobenzamide on The Inflammatory Responses of Lipopolysaccharide-induced Nephritic C57 Mouse
指導教授: 李銘亮
Li, Ming-Liang
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2004
畢業學年度: 92
語文別: 中文
論文頁數: 74
中文關鍵詞: 3-胺基苯甲醯胺脂多醣體腎病變的C57鼠一氧化氮第二型環氧
英文關鍵詞: 3-aminobenzamide, lipopolysaccharide, nephritic, C57 mouse, nitric oxide, cyclooxygenase-2
論文種類: 學術論文
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  • 將C57鼠每日由腹腔注射脂多醣體(lipopolysaccharide,LPS,120μg/25g C57鼠),連續注射14日,以建立由LPS所誘發C57鼠腎病變動物模式。經脂多醣體誘發C57鼠腎病變後,然後以3-胺基苯甲醯胺(3-aminobenzamide,3-AB,2.5 mg/25g C57鼠)口服給藥,連續16日後,發現腎病變鼠的尿蛋白,血清中肌酸酐、亞硝酸鹽/硝酸鹽(Nitrite / Nitrate)含量漸漸降低。C57鼠腎病變的腎清除功能亦恢復了近百分之九十。由脂多醣體誘發C57鼠腎病變的經3-胺基苯甲醯胺口服治療16日後,該C57鼠血清中腫瘤壞死因子(Tumor Necrosis Factor-α,TNF-α)、介白素(Interleukin-1β,IL-1β)及前列腺素E2 (Prostaglandinas E2,PGE2)含量也明顯降低。
    同時,病理檢查也顯示以口服3-胺基苯甲醯胺治療後的該C57鼠腎病變之腎組織,其髓過氧化物活性(Myeloperoxidase,MPO)也下降,一氧化氮合成(nitric oxide synthase,NOS)及環氧(Cyclooxygenase-2, COX-2)的表現也顯著降低。腎病變C57鼠的腎組織顯著減緩了腎病變期中腎絲球變大、膈細胞的增生。
    總結,口服3-胺基苯甲醯胺治療可明顯改善由脂多醣體所誘發C57鼠腎組織病變及腎功能衰退,其機轉可能是經由降低腎病組織一氧化氮合成及環氧(COX-2)的表現並降低發炎性細胞激素(cytokine)的生成而達成。

    To study the nephritis in mouse model, each of the C57 mouse was first injected with 120 μg lipopolysaccharide (LPS) intraperitoneally for 14 days. The abnormally higher urine protein content and serum creatinine level typical of nephritic manifestations were detected and maintained for at least 16 days after termination of LPS treatment in all LPS-induced nephritic C57 mice. These high levels of urine protein, nitrite/nitrate, serum creatinine, serum PGE2, serum IL-1β, and TNF-α of LPS-induced nephritic syndrome in C57 mice were gradually decreased following oral treatment with 3-aminobenzamide (3-AB, 2.5 mg/mouse) for 16 days. Concurrently, activities of myeloperoxidase(MPO), nitric oxide synthase (NOS) and cyclooxygenase-2 (COX-2) from extracts of LPS-induced nephritic kidneys were also decreased based on the MPO and SDS-PAGE evaluation, as well as 90% recovery of kidney’s clearance function. Considering all the experimental evidences found in this study, the lessening effect of antioxidant 3-AB on the severity of LPS-induced nephritic in C57 mice, was most likely coming from its ability to reduce the expression of NOS and COX-2.

    目錄 2 中文摘要 6 Abstract 8 壹、緒論 第一節 脂多醣體與敗血症和敗血性休克的簡介 9 第二節 一氧化氮的介紹 12 第三節 細胞激素與敗血性休克及腎臟疾病的關係 15 第四節 腎病變鼠的模式 16 第五節 3-胺基苯甲醯胺(3-aminobenzamide)的介紹 18 第六節 敗血性休克與誘發型一氧化氮合成及第二型環氧、前列腺素E2的關係 22 第七節 髓過氧化物(Myeloperoxidase,MPO)簡介 24 貳、研究目的 26 參、材料與方法 一、敗血症誘發腎病變動物模式 26 二、肌酸酐(Creatinine)濃度之測量 26 三、蛋白尿之測量 27 四、肌酸酐清除率之測定 28 五、血中及尿中NO2-/NO3-濃度測定 28 六、血清中腫瘤壞死因子(TNF-α)濃度測定 30 七、血清中介白素(IL-1β)濃度測定 30 八、前列腺素E2 (PGE2)的測定 31 九、口服3-胺基苯甲醯胺(3-aminobenzamide)藥物治療實驗 31 十、腎臟病理研究 32 十一、腎臟中髓過氧化物(Myeloperoxidase,MPO)活性的測定 33 十二、西方墨點法分析(Western Blot)腎臟中第二型環氧(COX-2)的表現 33 十三、西方墨點法分析(Western Blot)腎臟中一氧化氮合成的表現 34 肆、結果 37 伍、討論 39 陸、圖表 表一.腹腔注射不同劑量的脂多醣體對C57鼠的結果 44 表二.於腹腔注射脂多醣體後的C57鼠的死亡數目 45 圖一.不同劑量的脂多醣體與尿蛋白的濃度變化 46 圖二.不同劑量的脂多醣體與尿中肌酸酐的濃度變化 47 圖三.檢測由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理後之尿蛋白 48 圖四.檢測由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理後尿中肌酸酐 49 圖五.檢測由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理後血清中肌酸酐 50 圖六.由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理後對肌酸酐清除功能 51 圖七.檢測由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理後尿中Nitrite/Nitrate濃度 52 圖八.檢測由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理後血清中Nitrite/Nitrate濃度 53 圖九.由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理16日期間血清中介白素(IL-1β)變化 54 圖十.由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理16日期間血清中腫瘤壞死因子(TNF-α)變化 55 圖十一.檢測由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理後血清中前列腺素濃度 56 圖十二.由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理16日期間腎組織中髓過氧化物之含量變化 57 圖十三.由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理16日後腎組織中環氧(COX-2)含量 58 圖十四.由脂多醣體誘發腎病變之C57鼠於3-胺基苯甲醯胺治療處理16日後腎組織中一氧化氮合成含量 59 圖十五A. 正常的C57鼠腎組織 60 圖十五B. 注射脂多醣體誘發腎病變C57鼠之腎,其腎絲球有變大,膈細胞與內皮細胞有明顯增生 61 圖十五C. 以3-胺基苯甲醯胺治療由脂多醣體誘發腎病變之C57鼠,其腎組織腎絲球已恢復,膈細胞與內皮細胞發炎現象減緩 62

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