Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/13023
標題: Cytopiloyne receptor基因剔除可減弱streptozotocin誘發小鼠胰島beta細胞氧化壓力
Cytopiloyne receptor knockout attenuates streptozotocin-induced oxidative stress on islet beta-cell of mice
作者: 張惟雅
Chang, Wei-Ya
關鍵字: beta-cell;beta細胞;diabetes;reactive oxygen species;streptozotocin;糖尿病;活性氧化物;streptozotocin
出版社: 獸醫學系暨研究所
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摘要: 
由於胰島beta細胞抗氧化功能有限,慢性高糖會使胰島beta細胞內的活性氧化物(reactive oxygen species, ROS) 大量累積,致使beta細胞分泌胰島素的功能低下及凋亡。實驗室先前數據顯示了大花咸豐草(Bidens pilosa, BP) 萃取物cytopiloyne (CP),具有降低RIN-m5F細胞株高糖環境下的30-33% ROS生成及86-95%凋亡;並有效減緩第一型糖尿病NOD小鼠及第二型糖尿病db/db小鼠的糖尿病病程,包括降低NOD小鼠胰島細胞中83%-97%的免疫細胞浸潤、beta細胞的死亡和增加86-91%胰島素分泌;另外,CP也證實可降低50% db/db小鼠胰島beta細胞死亡和增加胰島素分泌。為確立上述CP抗糖尿病的相關機制,實驗室進一步篩檢出CP標的基因cytopiloyne receptor (CPR),並建立了CPR基因剔除實驗小鼠,本研究利用損害胰島beta細胞的藥劑streptozotocin (STZ) 在CPR基因剔除小鼠進行糖尿 病氧化緊迫致病機轉的研究;STZ主要作用機制為致使beta細胞DNA alkylation和提升細胞內氧化壓力。CPR基因剔除小鼠與同樣背景的C57BL/6小鼠(野生型小鼠) 在vehicle組中比較,可得到結果無明顯差異;STZ投予後, CPR基因剔除小鼠呈現的高血糖症狀(>200 mg/dl) 較野生型小鼠慢了4日、血清胰島素濃度也較高、胰臟胰島面積較完整且仍保留了62.6%,beta細胞內ROS表現程度也較野生型小鼠弱;因此我們推測CPR基因可能參與胰島beta細胞內ROS生成作用,進而緩減CPR基因剔除小鼠的STZ誘導型糖尿病病程;並可進一步推斷CP經由抑制beta細胞內CPR蛋白的活性或表現量以減緩NOD及db/db糖尿病小鼠的發病。藉此,期望未來可建立 CPR基因剔除小鼠成為新的糖尿 病實驗動物模式,來探索相關糖尿病基因等的轉譯醫學研究,與開發CP成為新穎結構之抗糖尿 病藥物,和現今臨床用藥達到相輔相成的功效。

Normal islet beta-cell has insufficient antioxidative function; therefore raised intracellular reactive oxygen species (ROS) level will make beta-cell dysfunction and/or apoptosis in chronic hyperglycemia. In our previous study, we found cytopiloyne (CP), a polyacetylenic glucoside from Bidens pilosa (BP), has the ability to reduce high glucose-induced 30-33% ROS expression and 86-95% apoptosis in beta-cell lines. Moreover, CP can also slow down mice diabetic process, including decreased immunocytes infusion, beta cell death and increased insulin secretion in both NOD and db/db mice (type 1 and 2 diabetes animal model). We screened out a CP receptor (CPR) target gene and established CPR knockout mice (CPR-/- mice) to study CP anti-diabetic mechanism. Furthermore, we used streptozotocin (STZ) to study oxidative stress-induced diabetes on CPR-/- mice. The mechanisms of STZ includes DNA alkylation and generating of ROS on beta-cell. We have been observed STZ-treated CPR-/- mice have significantly lower plasma glucose, higher serum insulin, better shape islet area and weaker beta-cell ROS level compared with wide type mice (WT mice). The results indicated that CPR may be involved in ROS synthesis in beta-cell to attenuate STZ-induced diabetes. And we deliberated that CP may inhibit CPR activity and / or expression to slow down NOD and db/db mice diabetes. In the future, the technologies of translation medicine study could help us to establish diabetic laboratory animal model and develop novel structure / function of the anti-diabetic drugs.
URI: http://hdl.handle.net/11455/13023
其他識別: U0005-2506201211071000
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