Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/52058
標題: 黃連素補充對第1型糖尿病非肥胖性小鼠免疫調節作用及其保護初代胰島細胞機制之研究
Effects of berberine supplementation on immunomodulatory functions in type 1 non-obese diabetes mice and the protective mechanism in primary pancreatic islet cells
作者: 闕維涵
Chueh, Wei-Han
關鍵字: berberine;黃連素;non-obese diabetes (NOD) mice;anti-inflammatory activities;immunomodulation;cytokines;primary islet cells;protective mechanism;非肥胖糖尿病小鼠;抗發炎活性;免疫調節;細胞激素;初代胰島細胞;保護機制
出版社: 食品暨應用生物科技學系所
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摘要: 
第1型糖尿病屬於自體免疫疾病,病患體內之免疫平衡傾向於Th1免疫反應而處於長期發炎狀態,此類發炎狀態可能增加對糖尿病併發症的不良影響。黃連素(berberine)屬於異喹啉類(isoquinoline)生物鹼,研究指出,黃連素具有許多藥理效用,包括降血脂及抗發炎等功效,但是黃連素對第1型糖尿病之影響仍不清楚,因此,本論文針對黃連素之抗發炎潛力進行研究,首先,探討黃連素補充對第1型糖尿病非肥胖性(non-obese diabetes, NOD)小鼠免疫調節作用之影響。NOD小鼠隨機分為以下四組,分別每日管餵以水取代黃連素的控制組(control, CO)、給予黃連素低(berberine low dose, BL, 50 mg/kg bw)、中(berberine medium dose, BM, 150 mg/kg bw)及高(berberine high dose, BH, 500 mg/kg bw)劑量組,並以正常小鼠ICR為品系對照(species control, SC)組,實驗進行14週。結果顯示,給予黃連素後,可顯著降低NOD小鼠脾臟細胞之Th1/Th2細胞激素分泌量比值;給予高劑量黃連素可顯著增加NOD小鼠脾臟細胞之抗發炎/促發炎細胞激素分泌量比值;給予黃連素後,可顯著增加NOD小鼠肝臟之抗發炎/促發炎細胞激素mRNA表現量比值,並顯著降低腎臟之促發炎/抗發炎細胞激素mRNA表現量比值。綜合以上結果,推測黃連素可經由調節NOD小鼠免疫平衡,使其傾向Th2免疫反應及抗發炎作用,而具有改善第1型糖尿病之潛力。由NOD小鼠體內胰島細胞數量結果發現,隨著黃連素給予劑量的增加,胰島細胞數量也隨之增加,具劑量反應關係。為探討黃連素是否可經由抗凋亡反應達到保護初代胰島細胞之效果,進行初代細胞實驗。結果顯示,於胰島細胞經STZ刺激前先添加黃連素,胰島細胞之抗凋亡/促凋亡基因(Bax/Bcl-2) mRNA表現量比值均顯著低於STZ刺激組,推測黃連素於胰島細胞受損前添加,可顯著抑制胰島細胞凋亡反應,達到預防胰島細胞凋亡之保護效果。

Type 1 diabetes (T1D) is one of autoimmune diseases. T1D patients having Th1-skewed immune responses result in chronic inflammation. The chronic inflammation may further deteriorate diabetic complications. Berberine is an isoquinoline alkaloid. Recently, berberine is reported to have many pharmacological functions, including hypolipidemic and anti-inflammatory effects. However, the effect of berberine on T1D is still not clear. Therefore, this study first investigated the effects of berberine supplementation in vivo on immunomodulatory functions, especially anti-inflammation, using type 1 non-obese diabetes (NOD) mice. The NOD mice were randomly divided into four groups, including control (CO) group which was intragastric gavage with water, berberine low dose (BL), berberine medium dose (BM) and berberine high dose (BH) groups which were respectively administrated with 50, 150, and 500 mg berberine/kg bw through 14 weeks by consecutive tube feeding. ICR mice were also selected as a species control (SC) group to compare with NOD mice (CO). The results showed that secretion ratios of Th1/Th2 cytokines by splenocytes of NOD mice significantly decreased after berberine supplementation. Secretion ratios of anti-/pro-inflammatory cytokines by splenocytes of NOD mice significantly increased after high-dose berberine supplementation. Furthermore, berberine administration increased ratios of anti-/pro-inflammatory cytokines mRNA expression in the liver but decreased the ratios of pro-/anti-inflammatory cytokines mRNA expression in the kidney of NOD mice. Overall, the results suggest that berberine supplementation may improve T1D symptoms via its potent anti-inflammatory and Th2-inclination activities. We found that berberine supplementation increased islet cell numbers of NOD mice in a dose-dependent manner, possibly via an anti-apoptotic pathway. To unravel the protective mechanism of berberine against apoptosis, we established in vitro experimental models using primary pancreatic islet cells from ICR mice. Results showed that berberine administration before streptozotocin (STZ)-stimulation significantly down-regulated ratios of pro-/anti-apoptotic genes (Bax/Bcl-2) expression (mRNA levels) in islet cells compared to those in STZ-stimulation alone group. We concluded that the protective mechanism of berberine on primary islet cells may be via its anti-apoptotic effect in a preventive manner.
URI: http://hdl.handle.net/11455/52058
Appears in Collections:食品暨應用生物科技學系

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