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  • 學位論文

n-3多元不飽和脂肪酸對敗血症小鼠免疫調節與發炎反應的影響

Effects of n-3 polyunsaturated fatty acids on immune modulation and inflammatory response in mice with polymicrobial sepsis.

指導教授 : 葉松玲

摘要


敗血症是由病原微生物感染引起的全身性發炎症狀,過度的發炎反應與輔助型T (helper T, Th)細胞與調節型T(regulatory T, Treg)細胞的失調在病程發展中扮演重要角色。n-3 polyunsaturated fatty acids (n-3 PUFA)具緩解發炎及免疫調節作用。本研究給予C57BL/6J小鼠富含n-3 PUFA飲食,探討n-3 PUFA對cecal ligation and puncture (CLP)誘發之敗血症造成Th與Treg細胞失衡及過度發炎的影響。動物隨機分成大豆油組與魚油組,n-3 PUFA佔總熱量依序為1.5%與3.9%,n-6/n-3 PUFA依序為7:1與2:1。連續餵食三週後進行CLP手術,分別於第零、一及三天犧牲。結果顯示,魚油介入可緩解術後體重流失、降低肺臟組織損傷、白血球浸潤、nuclear transcription factor-κB活化、tumor necrosis factor (TNF)-α與keratinocyte cell–derived chemokine mRNA的含量以及提升perioxisome proliferator activated receptorsγ mRNA的含量與蛋白質表現;降低血漿中interleukin (IL)-6與腹腔沖洗液中IL-6及TNF-α濃度。Th與Treg細胞調節部分,魚油可降低血液Th1、Th2及Th17細胞比例,增加Th1/Th2比值與降低腸繫膜淋巴結Th1與Treg轉錄因子T-bet和Foxp3 mRNA含量。綜合以上,當飲食中之n-6/n-3 PUFA為2:1,n-3 PUFA佔總熱量3.9%時,具調節敗血症之Th及Treg細胞分布、提升PPARγ表現、降低NF-κB活化,緩解發炎情形,減少肺臟受損及體重流失的作用。

並列摘要


Sepsis is a common cause of death in critically ill patients. Over-whelming inflammatory response and imbalance of helper T (Th) cells and regulatory T (Treg) cells are thought to be involved in the progression of sepsis. Previous studies showed that n-3 polyunsaturated fatty acids (PUFA) have both anti-inflammatory and immune-modulatory properties. This study investigated the effect of n-3 PUFA on the balance of Th subsets, Treg cells and inflammatory response in septic mice. C57BL/6J mice were randomly assigned to soybean oil (S) and fish oil (F) groups. The F group received a diet with 3.9% energy from n-3 PUFA and n-6/n-3 PUFA ratio was 2:1 whereas the S group contained 1.5% energy of n-3 PUFA and n-6/n-3 ratio was 7:1. After feeding for 3 weeks, sepsis was induced by cecal ligation and puncture (CLP) and mice were killed at day 0, 1, 3 respectively. The results showed that compared with S group, F group had lower inflammatory mediator levels in plasma and peritoneal lavage fluid after CLP. Also, F group had lower Th1, Th2, Th17 percentages and higher Th1/Th2 ratio in blood and lower T-bet and Foxp3 mRNA expressions in mesenteric lymph node. On the other hand, lymphocyte infiltration, nuclear transcription factor-κB (NF-κB) activation, and inflammatory mediator mRNA expression were reduced whereas both perioxisome proliferator activated receptors (PPAR) γ mRNA and protein expression were higher in lung tissues. The injury of lungs was also attenuated in the F group. The present findings suggest that n-3 PUFA rich diet with 3.9% energy from n-3 PUFA and n-6/n-3 PUFA ratio 2:1 may elicit a more balanced Th/Treg polarization, alleviate inflammatory responses, increase PPARγ, reduce NF-κB and inflammatory mediator expressions in lungs that may consequently attenuate the severity of sepsis-induced lung injury.

並列關鍵字

sepsis n-3 PUFA NF-κB helper T cell regulatory T cells

參考文獻


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