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脊椎損傷病人腦脊髓液中分子概況

脊椎損傷病人腦脊髓液中分子概況.

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脊椎損傷病人腦脊髓液中分子概況

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  1. 脊椎損傷病人腦脊髓液中分子概況 • Methylprednisolone (MP)，一種合成的醣皮質類固醇，是唯一美國藥物食品管理局 (FDA) 核准用於治療人類急性外傷性脊椎損傷 (acute traumatic spinal cord injury, SCI)。而 MP 用於治療脊椎損傷的作用被認為是在於抑制發炎反應。在本篇的論文，我們有興趣研究 MP 對於脊椎損傷病人腦脊髓液 (CSF) 中細胞激素的差異，研究族群包含三位未給予MP治療脊椎損傷病人、一位為完全損傷二位為未完全損傷病人、三位MP治療脊椎損傷病人及12位控制組病人。結果顯示在脊椎損傷後未給予MP處理的病人chemokine- 介白質素interleukine(IL)-8, 單核球趨化蛋白monocyte chemotactic proteins (MCP)-1和嗜中性球活化蛋白 neutrophil activating protein (NAP)-2, cytokine- IL-6, 轉移生長因子transforming growth factor-beta1 (TGF-1)]和內生性吸附分子intracellular adhesion molecule( ICAM)-1 明顯較高於MP處理及非脊椎損傷的病人，而利用電泳酵素分析法zymography分析未給予MP處理的病人基質金屬蛋白? matrix metalloproteinase-9 (MMP-9) 和金屬蛋白?組織抑制物tissue inhibitor of metalloproteinase-1 (TIMP-1) 的活性或濃度也是明顯較高於給予MP 處理及非脊椎損傷的病人，但是 MMP-2 則沒有顯著差異。給予 MP 治療的病人上皮生長因子 epidermal growth factor (EGF)與神經生長因子nerve growth factor (NGF) 的濃度較高於未給予 MP 治療的病人。且未給予MP的病人 soluble Fas 及 FasL的濃度有較高於 MP 處理及非脊椎損傷的病人。在in vitro實驗有一致的結果，MP具有抑制LPS刺激微膠細胞 microglia 趨化激素及細胞激素蛋白與 mRNA的表現。在微膠細胞EOC13.31， MP有意義的抑制 LPS 刺激 IL-27 次單位 p28 mRNA 的表現 (P=0.04)。此外MP亦可能藉由抑制所有測試之轉錄因子的表現進而抑制細胞激素的表現。且由病人的結果顯示脊椎損傷後所引起細胞激素的分泌是與脊椎損傷的嚴重程度(severity)具有相關性。然而近期研究指出Fas可以誘發單核球細胞 monocyte 及macrophage巨噬細胞促發炎反應細胞激素 proinflammatory cytokine 的產生且可以引發急性發炎反應及造成組織傷害，而我們結果指出MP具有抑制單核球細胞 Fas-ligation所引發促發炎細胞激素的分泌。結論顯示MP具有抑制脊椎損傷後發炎反應因子引發所造成組織的傷害。

  2. Molecular profiling of cerebrospinal fluid in patients with spinal cord injury • Methylprednisolone (MP), a synthetic glucocorticoid (GC), is the only therapeutic agent approved by the Food and Drug Administration (FDA) for the treatment of acute traumatic spinal cord injury (SCI) in humans. The therapeutic effects of MP in SCI are thought to inhibit inflammatory reaction. In this research, we investigate the cytokine profile in CSF collected from patients after SCI. Three patients without MP treatment after SCI, one of complete SCI (cSCI) and two of incomplete SCI (icSCI), three patients were MP treatment and twelve control patients were included. Our results suggests that patients with cSCI have higher expression of chemokine- interleukine-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and neutrophil activating protein-2 (NAP-2) and cytokine- IL-6, transforming growth factor-beta 1 (TGF-1), and intracellular adhesion molecule-1 (ICAM-1) than patients with MP treatment and control. Gelatin zymography analysis suggests that patients with cSCI have higher matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinase-1 (TIMP-1), but not MMP-2 activity than patients with MP treatment and control. Nerve growth factor (NGF) and epidermal growth factor (EGF) in patients with MP treatment were higher than patients without MP. Soluble Fas and soluble FasL were higher in patients without MP treatment as compared with patients of MP treatment and control. In vitro study, MP inhibits LPS induced chemokines and cytokines expression in EOC13.31, CHME3, and rat primary microglia cells. MP also siginificantly inhibits LPS induced IL-27 subunit p28 mRNA expression in microlia cells EOC13.31 (P=0.04). In addition, MP may inhibit cytokine expression through inhibit transcriptional factors expression. These results suggest that cytokine secretion after SCI is associated with severity of SCI. We demonstrate that MP inhibit Fas ligation induced pro-inflammatory cytokine secretion in monocyte. The conclusion showed that MP inhibited inflammatory response factors after tissue damage.

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