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  • 學位論文

沙棘葉萃取物對脂多醣誘發小鼠全身性發炎反應之影響

Sea Buckthron Leave extracts decrease Lipopolysaccharide-Induced systemic inflammatory response syndrome in C57BL/6 Mice

指導教授 : 劉凱莉

摘要


敗血症起因於體內感染,後續引起的全身性發炎反應,會使促發炎因子大量分泌產生惡病質。惡病質會引起低血壓且使血管受損,嚴重時會使組織供血不足。當組織供血不足會造成多重器官衰竭,包括:心臟衰竭或是肝衰竭。發炎相關疾病所造成的惡病質起因於訊息傳遞蛋白質或轉錄因子活化,促成蛋白質分解或減少蛋白質合成,使肌肉組織流失。因此,肌肉組織流失是肌肉蛋白質合成與降解失衡所造成的結果。肌肉組織流失有兩種蛋白質降解系統參與,其中包括泛素化蛋白酶體途徑和細胞自噬作用–溶酶體途徑。沙棘(Sea buckthorn)常用於治療心血管疾病、黏膜損傷以及皮膚疾病。過去研究得知沙棘葉萃取物具有抗菌、抗病毒以及抗腫瘤之活性,而沙棘葉在抗肌肉萎縮之功能仍是未知。所以本研究的目的主要是探討沙棘葉水萃萃取物與乙醇萃取物是否能預防敗血症所引起肌肉萎縮。實驗模式是分別將小鼠以沙棘葉水萃萃取物預處理兩週或用沙棘葉乙醇萃取物預處理四週,於空腹六小時後經腹腔注射脂多醣(1 mg/kg)誘發小鼠全身性發炎,十八小時後犧牲。脂多醣可以增加泛素化途徑和自噬作用活性,促進肌肉萎縮相關蛋白質表現增加。預處理沙棘葉萃取物後可避免脂多醣誘發骨骼肌之萎縮。本篇研究顯示,沙棘葉萃取物可抑制脂多醣誘發小鼠發炎反應中p38活化及NF-κB轉錄因子活性和抑制泛素化途徑及自噬作用路徑相關的蛋白質表現。進而減少蛋白質經由泛素化途徑及自噬作用途徑的流失,改善急性發炎疾病的惡病質誘發肌肉耗損。

並列摘要


Systemic inflammatory response syndrome (SIRS)is a serious and fatal disease in clinic. Lipopolysaccharide (LPS), derived from the cell wall of gram-negative bacteria, can induce a series of physiological or pathological changes resulting in septic shock and cause multiple organ dysfunctions. LPS-mediated endotoxinas well as a number of catabolic factors can cause severe inflammation and eventually lead to septic shock.Studies have shown that reactive oxygen species (ROS) is overproduced by the stimulation of LPS, and directly implicated as the second messengers in activation of NF-κB as well asmitogen-activated protein kinase (MAPK). Oxidants, free radicals and their derivatives also play important roles in the initiation and progression of skeletal muscle atrophy in various diseases states. The administration of antioxidants may attenuate myofiber atrophy in animal model. Muscle mass is the dynamic balance between the synthesis and degradation of muscle proteins. The rate of proteins degradation is more than biosynthesis which can cause muscle wasting.Two cellular proteolytic systems are involved in various of muscle atrophy including sepsis, which are the ubiquitin-proteasome pathway (UPP) and the autophagy- lysosomal pathway (ALP). Sea buckthorn (SBT, Hippophaerhamnoides Linn) is the popular herb used forcardiovascular diseases, mucosal injuries and skin disorders. Although the leaf extract of SBT have anti-bacterial, anti-viral and anti-tumor activities, the anti-muscle wasting effect of SBT leave is still unknown. In this study, we investigated the effects of water and ethanol extracts of SBT onLPS-induced muscle atrophy. Our results demonstrate thatmice was fed with water and ethanol extracts of SBT decreased LPS-induced skeletal muscle atrophy through theinhibition of UPP and ALP related atrophy-specific genes expression. Taken together, our findings suggest that SBT leave could prevent muscle wasting through the inhibition of UPP and ALP pathway.

參考文獻


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