透過您的圖書館登入
IP:3.137.185.180
  • 學位論文

利用靜磁場誘導內毒素耐受性以降低脂多醣引發之腦部傷害

Increment of endotoxin tolerance for reducing lipopolysaccharide induced brain injury by using static magnetic field

指導教授 : 黃豪銘

摘要


敗血症和神經退化性疾病都是由於發炎反應而造成腦部的傷害,目前均沒有有效的治療方式。因此以降低脂多醣造成全身的發炎反應,或是提升對於脂多醣的內毒素耐受性即成為抗感染治療的一個方向。可是要在腦部注射低劑量內毒素引發內毒素耐受性,其作用位置與注射劑量均很難控制。因此本研究探討在靜磁場(static magnet field, SMF)作用之下,對於接受內毒素注射的小鼠,其存活率和腦部病理切片是否有影響,此外並在有無靜磁場暴露之下,脂多醣對於BV-2微膠細胞的生長影響,及其誘導BV-2表現的細胞激素是否有差異。結果發現,靜磁場暴露能夠提升經脂多醣刺激小鼠的存活率,並減緩其小腦部位的發炎現象。而BV-2微膠細胞在受到靜磁場作用後,其生長數目會顯著低於未暴露磁場的細胞數量(p<0.05),且本研究發現暴露靜磁場的BV-2細胞,對於脂多醣誘導的毒殺作用,較之對照組亦有明顯的降低(p<0.05)。此外,以脂多醣刺激BV-2細胞的激素生成時,細胞會有類似內毒素耐受性的現象發生,尤其在暴露過靜磁場的細胞,其IL-6的生成量會明顯比未暴露靜磁場的細胞來的低(p<0.05)。這些結果均顯示,靜磁場可以誘導內毒素耐受性的發生,並因此降低脂多醣對於腦部的發炎反應以及傷害。

並列摘要


The effective method for preventing brain-damage and neurodegeneration caused by inflammation is still limited. Down-expression of the lipopolysaccharide (LPS)-induced inflammatory cytokines and thus resulting in endotoxin tolerance was reported to be a new aspect for anti-infection treatment. However, since the dosage and action site are hard to control, endotoxin tolerance caused by low-dose LPS injection in brain tissue may induce side effects. The aim of this study was to test the hypothesis whether static magnetic field (SMF) can be a stimulation source for inducing endotoxin tolerance in brain tissue. This study, examined survival rate and brain tissue changes of LPS-challenged mice, pre-treated with or without SMF. In addition, the effects of SMF exposure on growth rate and cytokines expression of LPS-challenged BV-2 microglia cells were monitored. Our results showed that SMF pre-exposure had positive effects on the survival rate and histological outcomes of LPS-treated mice. Furthermore, SMF pre-exposure significantly increased IL-6 expression of BV-2 cell (p<0.05) and resulted in a significant reduction (p<0.05) of cytotoxicity in LPS treated cells. According to these results, although more advanced experiments are needed, it is reasonable to suggest that SMF has potential to be an alternative simulation source for inducing endotoxin tolerance in brain tissue.

參考文獻


Lin CT, Chen CA, Chen YF, Chen CY, Lee SY, Huang HM. A static magnetic field reduced lipopolysaccharide-induced proinflammatory cytokine level of fibroblasts by altering membrane fluidity. J Dent Sci, 2: 11-18, 2007.
Aderka D, Le J, Vilcek J. IL-6 inhibits lipopolysaccharideinduced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. The Journal of Immunology, 143: 3517-3523, 1989.
Aloisi F. The role of microglia and astrocytes in CNS immune surveillance and immunopathology. Adv Exp Med Biol, 468: 123-133, 1999.
Ashdown H, Poole S, Boksa P, Luheshi GM. Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats. Am J Physiol Regul Integr Comp Physiol, 292: 1667-1674, 2007.
Bakhshi S, Arya LS. Etiopathophysiology of disseminated intravascular coagulation. J Assoc Physic India, 51: 796-800, 2003.

延伸閱讀