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系統識別號 U0007-1907201821432000
論文名稱(中文) 枸杞多醣體與藻藍素對阿斯匹靈誘導大鼠胃黏膜細胞RGM-1損傷之修復影響
論文名稱(英文) Effects of Lycium babarum polysaccharides and C-phycocyanin on healing of aspirin-induced damage in rat gastric mucosal RGM-1 cells
校院名稱 臺北醫學大學
系所名稱(中) 保健營養學研究所
系所名稱(英) Graduate Institute of Nutrition and Health Sciences
學年度 106
學期 2
出版年 107
研究生(中文) 王詩雅
研究生(英文) Shih-Ya Wang
學號 Ma07105011
學位類別 碩士
語文別 中文
口試日期 2018-07-02
論文頁數 98頁
口試委員 委員-蔡英傑
委員-楊素卿
指導教授-趙振瑞
中文關鍵字 胃黏膜損傷  阿斯匹靈  枸杞多醣體  藻藍素 
英文關鍵字 gastric mucosa damage  aspirin  Lycium barbarum polysaccharides  C-phycocyanin 
學科別分類
中文摘要 2011年台灣胃潰瘍盛行率為4.7%,而潰瘍的發生與黏膜障壁防禦功能降低有關,其中非類固醇抗發炎藥物的使用為造成黏膜障壁防禦功能降低的主因之一,其會增加活性氧屬生成,進而誘發胃損傷。而枸杞為一中藥材,其主要活性成份為枸杞多醣體(Lycium barbarum polysaccharides, LBP)。C型藻藍素(C-phycocyanin, C-Pc)則是由螺旋藻(Spirulina platensis)衍生的主要藻膽色素蛋白質,為具抗氧化能力的天然色素。故本研究欲探討預先添加不同濃度之LBP (100、300及800 μg/mL)或/與螺旋藻萃取物(30、250及750 μg/mL)培養24小時,對於aspirin所造成之大鼠胃黏膜RGM-1細胞損傷,是否能透過降低氧化傷害與抑制發炎反應之特性而達到修復胃黏膜損傷的效果。結果顯示,RGM-1細胞經25 mM aspirin誘發3小時後,NF-κB (p 65)與DNA之結合、iNOS活性、MDA、PGE2、mucin 1及EGF濃度相較於控制組皆顯著上升,SOD活性相較於控制組則顯著下降。然而,預先添加枸杞多醣(300 μg/mL)則可減輕因aspirin所誘發之細胞內iNOS活性上升,達到抗發炎之效果;而預先添加螺旋藻萃取物(30 μg/mL)除了亦能減輕因aspirin所誘發之細胞內iNOS活性上升,同時也可降低細胞內MDA之生成,達到抗發炎與降低氧化壓力之效果。也因此,此兩添加物進而預防非類固醇抗發炎藥物所造成之RGM-1細胞損傷,使得PGE2、MUC1及EGF等胃黏膜保護因子之表現較趨近於正常。
英文摘要 Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the major risk factor for the development of gastric ulcer. Lycium barbarum polysaccharides (LBP) have been reported to have antioxidation, immunomodulation, and regeneration actions. C-phycocyanin (C-Pc) is a major biliprotein pigment of Spirulina platensis. C-Pc has a variety of regulatory functions including antioxidation, anti-inflammation, and wound healing properties. The objectives of this study were to investigate the pre-treatment effects of LBP (100,300 and 800 μg/mL) and/or Spirulina extract (30, 250 and 750 μg/mL) for 24 hours on healing of aspirin-induced injury in rat gastric epithelial cell line RGM-1. The results showed that the incubation of 25 mM aspirin for 3 hours significantly increased the activities of NF-κB (p 65) DNA binding and iNOS, and concentrations of MDA, PGE2, mucin 1 and EGF. In addition, 25 mM aspirin significantly decreased SOD activity. The activity of iNOS was significantly inhibited by LBP (300 μg/mL) and Spirulina extract (30 μg/mL). Pretreatment with Spirulina extract (30 μg/mL) also significantly attenuated MDA production. Therefore, the pretreatment of LBP or C-Pc attenuates damage of RGM-1 cells induced by 25 mM aspirin, and returns concentrations of PGE2, MUC1 and EGF closer to normal status.
論文目次 目錄
中文摘要 I
Abstract II
致謝 III
圖目次 VIII
表目次 IX
第一章 緒論 1
第二章 文獻回顧 5
第一節 胃的功能與結構 5
第二節 胃潰瘍 6
一、胃潰瘍之成因 6
二、NSAIDs使用與胃損傷之關聯性 9
第三節 胃黏膜表皮細胞 13
一、胃黏膜表皮細胞 13
二、大鼠胃黏膜表皮細胞(RGM-1) 16
第四節 調控胃潰瘍之因子 19
一、發炎因子與胃潰瘍 19
二、氧化壓力與胃潰瘍 20
三、細胞保護因子與胃黏膜 21
第五節 枸杞與枸杞多醣、藻藍素及其相關研究 23
一、枸杞之簡介 23
二、枸杞多醣之組成 23
三、枸杞多醣之相關研究 27
四、藻藍素之簡介 28
五、藻藍素之相關研究 30
第六節 研究目的與動機 32
第三章 實驗材料與方法 33
第一節 實驗材料 33
一、實驗細胞株 33
二、枸杞萃取物 33
三、藻藍素萃取物 34
第二節 細胞培養與實驗設計 37
一、細胞培養 37
二、實驗設計 37
第三節 分析項目與方法 40
一、枸杞多醣萃取物之單醣組成分析 40
二、細胞存活率分析-MTS assay 40
三、發炎性指標之測定 41
(一)iNOS之活性 41
(二)COX-2之濃度 42
(三)NF-κB (p 65)與DNA結合之活性 43
四、氧化性指標之測定 45
(一)MDA之濃度 45
(二)SOD之活性 46
五、細胞保護因子之測定 47
(一)PGE2之濃度 47
(二)黏膜修復因子(MUC1)之濃度 48
(三)EGF之濃度 49
第四節 統計分析 50
第四章 結果 51
第一節 枸杞多醣萃取物之單醣組成分析 51
第二節 細胞存活率分析-MTS assay 54
一、Aspirin對細胞存活率之影響 54
二、LBP對細胞存活率之影響 54
三、C-phycocyanin對細胞存活率之影響 55
第三節 發炎性指標之測定 57
一、iNOS之活性 57
二、COX-2之濃度 59
三、NF-κB (p 65)與DNA結合之活性比 61
第四節 氧化性指標之測定 63
一、MDA之濃度 63
二、SOD之活性 65
第五節 細胞保護因子之測定 67
一、PGE2之濃度 67
二、黏膜修復因子MUC1之濃度 69
三、黏膜修復因子EGF之濃度 71
第五章 討論 73
第一節 劑量探討 73
一、胃黏膜上皮細胞損傷誘發之aspirin劑量 73
二、LBP添加對細胞存活率之影響 74
三、C-Pc添加對細胞存活率之影響 75
第二節 LBP與C-Pc對發炎性指標之影響 76
第三節 LBP與C-Pc對氧化性指標之影響 79
第四節 LBP與C-Pc對胃黏膜保護因子之影響 81
一、PGE2 81
二、mucin 1 (MUC1) 82
三、EGF 84
第五節 綜合討論 86
第六章 結論 89
第七章 參考文獻 90

圖目次
圖一、胃黏膜之動態平衡與造成胃潰瘍之因子 8
圖二、NSAIDs之作用機制與其副作用 11
圖三、NSAIDs造成胃損傷與出血之病理機制 12
圖四、胃黏膜結構 15
圖五、RGM-1細胞之型態觀察 18
圖六、藻藍素(phycocyanin)與膽綠素(biliverdin)之化學結構相似 29
圖七、細胞培養實驗流程圖 39
圖八、以HPAEC-PAD分析LBP單糖組成之圖譜 52
圖九、Aspirin、LBP及C-Pc對RGM-1細胞存活率之影響 56
圖十、Aspirin、LBP及C-Pc對RGM-1細胞中發炎性指標iNOS活性之影響 58
圖十一、Aspirin、LBP及C-Pc對RGM-1細胞中發炎性指標COX-2濃度之影響 60
圖十二、Aspirin、LBP及C-Pc對RGM-1細胞核中發炎性指標NF-κB (p 65)活性之影響 62
圖十三、Aspirin、LBP及C-Pc對RGM-1細胞中氧化壓力指標MDA濃度之影響 64
圖十四、Aspirin、LBP及C-Pc對RGM-1細胞中抗氧化指標SOD活性之影響 66
圖十五、Aspirin、LBP及C-Pc對RGM-1細胞培養液中PGE2濃度之影響 68
圖十六、Aspirin、LBP及C-Pc對RGM-1細胞中mucin 1濃度之影響 70
圖十七、Aspirin、LBP及C-Pc對RGM-1細胞培養液中EGF濃度之影響 72

表目次
表一、枸杞(L. barbarum)之多醣組成 25
表二、枸杞(L. barbarum)之單醣組成 26
表三、枸杞多醣萃取物之分析報告表 36
表四、枸杞多醣萃取物之單醣組成 53
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