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研究生:陳郁臻
研究生(外文):Chen, Yu-Jhen
論文名稱:自然殺手細胞改善 Streptozotocin 誘發糖尿病小鼠發炎反應與胰島素阻抗之影響
論文名稱(外文):The Effects of Natural Killer Cells on Inflammation and Insulin Resistance in Streptozotocin - Induced Diabetic Mice
指導教授:龔瑞林龔瑞林引用關係
指導教授(外文):Kong, Zwe-Ling
口試委員:鄧文炳黃效民吳亮宜林翰佳陳榮祥
口試委員(外文):Deng, Win-PingHwang, Shiaw-MinWu, Liang-YiLin, Han-JiaCheng, Ron-shan
口試日期:2016-06-24
學位類別:碩士
校院名稱:國立臺灣海洋大學
系所名稱:食品科學系
學門:農業科學學門
學類:食品科學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:43
中文關鍵詞:自然殺手細胞糖尿病胰島素阻抗發炎
外文關鍵詞:Natural Killer CellsDiabetic mellitusInsulin ResistanceInflammation
相關次數:
  • 被引用被引用:1
  • 點閱點閱:63
  • 評分評分:
  • 下載下載:2
  • 收藏至我的研究室書目清單書目收藏:0
糖尿病 (Diabetic mellitus, DM) 為一種新陳代謝異常之疾病,其成因多為胰島素分泌不足或無法分泌,及胰島素阻抗 (Insulin resistance, IR) 所導致。當體內的免疫細胞失調會促使發炎反應加劇,進而使得 IR 變嚴重。自然殺手細胞 (Natural killer cells, NK cells) 為人體第一道免疫防禦系統,參與體內的非專一性細胞毒殺作用,當外來物侵入體內時,其可啟動免疫防禦作用。已有實驗證實高血糖的狀態下,NK cells 的表面抗原 NKG2D 、 NKp46 的數量較健康者要來的少,導致 NK cells 的毒殺能力下降。因此本研究將探討注射 NK cells 下,對於以 Streptozotocin (STZ) 誘發之 DM 小鼠其改善發炎與 IR 之作用影響。本實驗選用雄性五週齡 BALB/c 小鼠,以 STZ 誘發成 DM,並給予餵食 45 % 高脂飲食維持糖尿病病況,在於第九週進行尾靜脈注射 NK cells,每兩天給予一次 1 ×106 cells NK cells,共給予三次。實驗結果證實注射後之 NK cells ,會移動至脾臟組織,其可改善 IR 及發炎之功效是透過降低促發炎型細胞激素腫瘤壞死因子-α (tumor necrosis factor-α, TNF-α) 及介白素-6 (Interleukin-6, IL-6),其抑制 IL-6-STAT3 軸之反應路徑及減少 TNF-α 可降低發炎反應路徑蛋白 pJNK 的表現,達到抑制發炎及提升胰島素傳訊路徑,達成改善糖尿病患者 IR 及發炎之現象。
Diabetic mellitus (DM) is metabolic disorder, it is develops because of inadequate islet β-cell or insulin resistance (IR). Immune dysfunction disorder will cause the increase of the inflammation and IR. Natural killer cells (NK cells) involve in of non-specific toxic effect. The evidence revealed that the number of healthy NK cells surface antigen NKG2D and NKp46 are higher than diabetes under hyperglycemic conditions. This study aims to investigate NK cells improve IR and inflammation in streptozotocin (STZ) induced diabetic mice. The method was used intraperitoneal injection STZ (90 mg/kg) induced diabetes in five weeks olds BALB/c male mice and fed 45% high fat diet for six weeks. The results adoptive transfer NK cells (1 ×106 cells/0.1mL / once in two day) improved glucose tolerance and IR. Adoptive transfer of NK cells is capable of improving IR through regulating cytokines. Injection of NK cells decreased tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentration in liver. Decreasing in TNF-α results in the lowering of pJNK expression which improve inflammation and IR . Lower amount of IL-6 contribute to increase pAKT enhancing insulin signal. Result suggested that injection of NK cells may attenuated inflammation and IR in diabetic mice.
摘要 I
Abstract II
目錄 III
名詞縮寫 V
圖目錄 VI
表目錄 VII
附錄目錄 VIII
壹、 緒論 1
貳、文獻回顧 2
一、糖尿病 2
1 胰島素運作機制 2
2 胰島素阻抗與糖尿病 2
3 糖尿病 3
二、自然殺手細胞 5
1 自然殺手細胞 5
2自然殺手細胞與糖尿病 5
三、巨噬細胞 5
1巨噬細胞與自然殺手細胞 5
2 巨噬細胞與發炎反應 6
3 發炎反應與胰島素阻抗 6
參、實驗材料 7
一、實驗動物 7
二、動物飼料 7
三、實驗藥品 7
1 細胞實驗 7
2 動物實驗 8
四、儀器設備 9
肆、實驗方法 10
一、動物實驗 10
1 動物飼養與分組 10
2 糖尿病誘導 11
3 糖尿病相關分析 11
4 注射自然殺手細胞 12
5 巨噬細胞及細胞激素分析 13
6 分析樣品 14
7 統計分析 18
伍、實驗結果 19
陸、討論 22
柒、結論 24
捌、參考文獻 25
玖、圖表 27
拾、附錄 39



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