維生素D減緩大鼠缺血性腦損傷之新作用機轉

Taipei Medical University Institutional Repository > 營養學院 > 保健營養學系暨研究所 > 博碩士論文 > Item 987654321/61159

請使用永久網址來引用或連結此文件: http://libir.tmu.edu.tw/handle/987654321/61159

題名:	維生素D減緩大鼠缺血性腦損傷之新作用機轉 A novel mechanism of vitamin D-mediated protection against cerebral ischemie injury in rats
作者:	龔酩雅 Kung, Ming-Ya
貢獻者:	保健營養學研究所吳啓豪
關鍵詞:	缺血性中風;維生素D;類鐸受體;發炎體;IL-1β schemic stroke;Vitamin D;Toll-like receptor;inflammasome;IL-1β
日期:	2016
上傳時間:	2021-11-26 19:56:29 (UTC+8)
摘要:	臨床上80 %之中風患者屬於缺血性中風 (ischemic stroke)，已知缺血性中風會誘發類鐸受體 (toll-like receptor, TLR)與發炎體 (inflammasome)活化，進而刺激發炎因子釋放，造成腦組織發炎反應。臨床研究顯示，體內維生素D濃度高低可能與罹患中風的風險有關並影響中風患者之預後，然而其作用機轉是否與TLR (Toll-like receptor)或發炎體有關仍有待釐清。本研究擬探討維生素D對於腦缺血再灌流損傷之保護作用及可能分子機轉，實驗採用8週齡雄性SD大鼠，分為四組分別為 (一) 控制組 (sham) (二) 缺血再灌流組 (ischemia/reperfusion, I/R) (三) 維生素D缺乏組 (vitamin D deficiency, VDD)，以飼料餵14天 (四) 維生素D補充組 (vitamin D supplements, VDS )，給予0.7 μg/kg維生素補充劑施打8天，然後施予中大腦動脈梗塞 (middle cerebral artery occlusion, MCAO)手術，並於術後90分鐘恢復供血，探討補充與剝奪維生素D對於腦損傷及上述分子表現之影響。實驗結果顯示，相較於I/R組維生素D缺乏可增加腦損傷嚴重程度，促進脂質過氧化產物丙二醛 (malondiadehyde, MDA)累積與發炎激素IL-1β (Interleukin-1 beta)分泌，補充維生素D可改善上述的作用。西方點墨法分析顯示，缺乏維生素D會增加TLR2-MyD88-NF-κB signaling cascade表現和NLRP3 發炎體的活化促使pro-caspase-1轉變為cleaved caspase-1，活化IL-1β。然而，補充維生素D可抑制TLR2和NLRP3發炎體相關蛋白質表現外，此外，維生素D補充還可活化TLR10-PI3K-AKT訊息傳遞路徑，抑制發炎反應。綜合上述，補充維生素D可降低腦缺血再灌流氧化損傷，並藉由抑制TLR2與發炎體活化之作用以減少促發炎因子IL-1β之成熟，此外，還可活化TLR10訊息傳遞路徑，進而抑制發炎反應，達到保護腦缺血再灌流損傷之作用。 Ischemic stroke accounts for almost 80% of the clinical stroke. Ischemic stroke cause severe brain inflammation, and pro-inflammatory cytokines secretion through the activation of toll-like receptor and inflammasome. Clinical studies indicate that the level of vitamin D concentration is associated with higher risk of stroke. However, the molecular mechanism is remain unclear. This study aimed to investigate the protective action of vitamin D on cerebral ischemia-reperfusion injury and the possible molecular mechanism. Eight-weeks-old male Sprague-Dawley rats were assigned to (1) control group (sham) ; (2) ischemia/reperfusion group (I/R) ; (3) vitamin D deficiency group (VDD group) : dietary deprivation of vitamin D for 14 days ; (4) vitamin D supplements group (VDS group) : 0.7μg /kg vitamin D supplements for 8 days. Middle cerebral artery occlusion (MCAO) was performed with SD rats, and 90 mins late to initiate reperfusion to investigate the effect of vitamin D supplements and deprivation to the brain damage and the performance of relational molecular. Results showed that vitamin D deficiency increased the severity of brain damage, lipid peroxidation products MDA accumulation and pro-inflammatory cytokines release. In contrast, vitamin D supplements improved brain damage. Western blot indicated that vitamin D deficiency may active TLR2-MyD88-NF-κB signaling cascade and NLRP3 inflammasome induce cleaved caspase-1 protein expression, increase IL-1β secretion. However, vitamin D can inhibit TLR2 and NLRP3-related protein expression. Besides, vitamin D can inhibit inflammation through the activation of TLR10-PI3K-AKT signaling pathway.In conclusion, Vitamin D might reduce cerebral ischemic-reperfusion oxidative damage and inflammation by inhibited activation of TLR2, reduced the mature of pro-inflammatory factor IL-1β and activation of TLR10 to protect against cerebral ischemia-reperfusion injury.
描述:	碩士指導教授：吳啓豪
資料類型:	thesis
顯示於類別:	[保健營養學系暨研究所] 博碩士論文

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
index.html		0Kb	HTML	74	檢視/開啟

檢視Licence

在TMUIR中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....