- 學位論文
草莓研磨粉經由調節氧化壓力以延緩indomethacin誘導之大白鼠胃潰瘍
Strawberry powder alleviates indomethacin-induced rat gastric ulcer via regulating oxidative status and inflammatory responses
摘要
許多學者研究發現草莓含有豐富多酚成分，又許多報告顯示草莓似乎透過活化細胞抗氧化酶提供間接抗氧化保護的功用，多酚成分在抗氧化保護功用佔有重要的地位，因此本研究將探討草莓是否可保護藥物引起的細胞傷害。Indomethacin是一種非類固醇抗炎藥物Non-Steroidal Anti-Inflammatory Drug，簡稱NSAID，在醫療上用於緩解疼痛和炎症。以前的研究指出NSAID這類藥物會引起胃腸黏膜損傷，並且與發炎、氧化壓力及細胞凋亡有相關性。本研究的目的是探討草莓對Indomethacin誘導的胃潰瘍是否有保護功能。實驗先將SD大鼠餵三種濃度50mg/kg、100mg/kg、150mg/kg的草莓粉溶液，每日餵食一次共5天，再餵Indomethacin 35mg/kg，經過四小時後將老鼠犧牲，然後切下胃比較胃潰瘍狀況。實驗結果顯示，50mg/kg組沒有保護作用，並可發現胃黏膜有細胞損傷，100mg/kg組有部分的保護。150mg/kg組在組織病理方面，巨觀觀察及切片染色結果一致，並無發現明顯細胞損傷。我們進一步探討其機轉，首先，我們檢測胃黏膜細胞的PGE2濃度，結果發現150mg/kg草莓可以防止PGE2濃度下降，由此可以防止胃酸分泌，減少潰瘍的發現，同時我們也發現，餵養150mg/kg 草莓在免疫組織化學染色中COX-2的表現增加、TNF-α的表現則明顯減少。在檢測NFkB、Bcl-2、Bax、BaK中也顯示，草莓預防胃黏膜的細胞凋亡現象；MDA、Catalase、GSH測定結果也顯示草莓對於氧化壓力具有預防的效果。由結果推測，草莓防止藥物引起大鼠的胃潰瘍，主要經由四大系統，(一)經由COX-2/PGE2之相關的途徑去抑制胃酸的分泌，(二)透過抑制TNF-α來阻斷發炎反應，(三) Bcl-2和Bak之間的平衡，在細胞凋亡中決定細胞生存或凋亡，(四) 草莓激活細胞抗氧化提供保護黏膜的功用。因此適量食用草莓多酚能有效預胃潰瘍。
並列摘要
Many investigators found strawberries include rich polyphenols and many reports showed that strawberry with indirect antioxidant protection by activating cellular antioxidant enzymes. Rich polyphenols play an important role in antioxidant protection. Therefore, our study aims to explore whether strawberries could against drugs-induced cell damage. Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) commonly used to reduce pain and inflammation. Previous studies showed that NSAIDs caused gastrointestinal mucosal injury and associated with inflammation, oxidative stress and apoptosis. The aim of our study was to investigate the protection effects of strawberries against Indomethacin-induced gastric ulcer. The SD rats were treated with three doses of strawberry extract (50, 100 or 150 mg/kg) once a day for 5 days and then treated with Indomethacin (35mg/kg). Rats were sacrificed after 4 hours and collection of stomach. Our result showed that the high dose (150 mg/kg) of strawberry extract reduced cell damage more than those with lower doses (50 and 100 mg/kg) of strawberry extract by macroscopic analysis. We further explored the underlying mechanisms. Our result showed that the high dose (150 mg/kg) of strawberry extract reversed the decrease of PGE2 more than those with lower doses (50 and 100 mg/kg) of strawberry extract. The high dose (150 mg/kg) of strawberry extract enhanced the expression of COX-2, NFkB and Bcl-2, and reduced the expression of TNF-α, Bax and BaK. The high dose (150 mg/kg) of strawberry extract further decreased the expression of MDA and increased the expression of Catalase and GSH. Our results suggested that strawberry attenuate Indomethacin-induced gastric ulcer in rats through mechanisms that involve (1) up-regulating the COX-2/PGE2 pathway to inhibit gastric acid secretion (2) inhibition of TNF-α to inhibit inflammation (3) antiapoptotic potential (4) activating cellular antioxidant enzymes. Therefore, moderate consumption of strawberry polyphenols is associated with reduced risk of ulcer.