草莓葉乙醇萃取物對調控脂多醣誘發C57BL/6J小鼠發炎反應及肌肉耗損之功效

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草莓叶乙醇萃取物对调控脂多醣诱发C57BL/6J小鼠发炎反应及肌肉耗损之功效

Effect of the strawberry leaf ethanol extract on lipopolysaccharide-induced inflammatory response and muscle wasting in C57BL/6J mice

颜玉佩 , 硕士　　导师：刘德中　　

繁体中文

草莓叶；脂多醣(LPS) ； UPP路径；肌肉耗损；促发炎细胞因子； strawberry leaves ； lipopolysaccharide ； ubiquitin-proteasome pathway ； muscle atrophy ； pro-inflammatory cytokines

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摘要 │ 参考文献 (100) │ 国际计量

摘要〈TOP〉

脂多醣(Lipopolysaccharide, LPS)为革兰氏阴性菌细胞壁的主要成分，先前研究证实，LPS会诱发小鼠生成大量促发炎媒介物，导致体内器官发炎，亦会活化泛素‐蛋白酶体途径(ubiquitin-proteasome pathway, UPP)、自噬‐溶酶体途径(autophagy-lysosome pathway, ALP)及Caspase-3，增加骨骼肌蛋白质分解，使肌肉萎缩。文献指出，草莓叶萃取物可抑制发炎、增加抗氧化酵素及降低脂质过氧化，而本研究将探讨草莓叶乙醇萃取物是否能抑制LPS诱发的发炎反应及肌肉萎缩。C57BL/6J小鼠灌食灭菌水或草莓叶乙醇萃取物 (500 mg/kg)，每周3次，持续2周後，在小鼠腹腔内注射LPS，18小时後牺牲。研究结果显示，草莓叶乙醇萃取物可以改善LPS造成脾脏肿大，降低血液、肝、脾、肺脏及副睾脂肪促发炎媒介物tumor necrosis factor-alpha、interleukin-6、interleukin-1 beta、monocyte chemoattractant protein-1、inducible nitric oxide synthase、cytochrome c oxidase-2生成，并减少红血球glutathione耗损、红血球及肝脏malondialdehyde的生成，同时降低肝脏nuclear factor erythroid 2-related factor 2的表现。灌食草莓叶乙醇萃取物可显着改善LPS诱发胫前肌 myosin heavy chain蛋白质及胫前肌重量的减少。灌食草莓叶乙醇萃取物亦可减少LPS诱发UPP路径中 muscle atrophy F-box与muscle RING finger protein 1表现及Caspase-3活性。此外，草莓叶乙醇萃取物处理可减少LPS诱发肌肉组织inhibitor kappa B-α、inhibitor kappa B kinaseα/β、mitogen-activated protein kinases (MAPKs)的磷酸化及NF-κB p65、forkhead box protein O 1核蛋白的表现量。综合以上实验结果可知，补充草莓叶乙醇萃取物可经由抑制MAPKs、NF-κB和FoxO1活化，显着改善LPS诱发的发炎反应，减少蛋白质分解相关分子的表现，改善LPS诱发之骨骼肌肉耗损。

并列摘要〈TOP〉

Lipopolysaccharide (LPS), a main component of the cell wall of Gram-negative bacteria, could increase pro-inflammatory mediator production which result in organ inflammation. Data have shown that LPS through activation of ubiquitin-proteasome pathway (UPP), autophagy-lysosome pathway, Caspase-3, causes skeletal muscle protein degradation and then muscle atrophy. Strawberry leaf extracts can suppress inflammation and lipid peroxidation as well as increase antioxidant enzyme expression. The aim of this study was to investigate the inhibitory effect of strawberry leaf ethanol extract on LPS-induced inflammatory response and muscle atrophy. C57BL/6J mice were given dd water or strawberry leaf ethanol extract (500 mg/kg, 150 μl/mouse by intragastric gavage, every other day), three times a week for two weeks, then sacrificed after intraperitoneal injection of LPS eighteen hours. Strawberry leaf ethanol extract can significantly decrease LPS-induced spleen enlargement as well as pro-inflammatory mediator tumor necrosis factor-alpha, interleukin-6, interleukin-1 beta, monocyte chemoattractant protein-1, inducible nitric oxide synthase, cytochrome c oxidase-2 production in plasma, liver, spleen, lung and epididymis adipose tissue, glutathione depletion and malondialdehyde (MDA) production in RBC as well as MDA production and nuclear factor erythroid 2-related factor 2 reduction. Notably, supplementation with strawberry leaf ethanol extract could decrease LPS-induced depletion of myosin heavy chain expression and tibialis anterior muscle weight. Strawberry leaf ethanol extract significantly decreased LPS-induced expression of UPP related protein, muscle F-box 1, muscle RING finger protein 1, and caspase-3 activity that result in decrease of protein degradation and muscle atrophy in LPS treated mice. Moreover, strawberry leaf ethanol extract significantly diminished LPS-induced phosphorylation of inhibitor kappa B, inhibitor kappa B kinase, mitogen-activated protein kinases (MAPKs) as well as NF-kB p65 and forkhead box protein O 1 nuclear protein expression. In summary, supplementation of strawberry leaf ethanol extract significantly lessened LPS-induced inflammation and muscle atrophy which is related to its inhibitory effect on LPS-induced activation of MAPKs, NF-kB and FoxO1 as well as protein degradation pathways.

参考文献 ( 100 ) 〈TOP〉

1. Newton K, Dixit VM. Signaling in innate immunity and inflammation. Cold Spring Harb Perspect Biol 2012;4(3).
连结：
2. Voisin L, Breuillé D, Combaret L, et al. Muscle wasting in a rat model of long-lasting sepsis results from the activation of lysosomal, Ca2+-activated, and ubiquitin-proteasome proteolytic pathways. Journal of Clinical Investigation 1996;97(7):1610.
连结：
3. Schakman O, Dehoux M, Bouchuari S, et al. Role of IGF-I and the TNFalpha/NF-kappaB pathway in the induction of muscle atrogenes by acute inflammation. Am J Physiol Endocrinol Metab 2012;303(6):E729-39.
连结：
4. Doi K, Leelahavanichkul A, Yuen PS, Star RA. Animal models of sepsis and sepsis-induced kidney injury. J Clin Invest 2009;119(10):2868-78.
连结：
6. Bosmann M, Ward PA. The inflammatory response in sepsis. Trends Immunol 2013;34(3):129-36.
连结：

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使用DOI作为永久连结

引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。