Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/12844
標題: 白藜蘆醇對奧氮平誘導代謝異常之C57BL/6JNarl小鼠的影響
Beneficial effects of resveratrol on olanzapine-induced metabolic abnormalities in C57BL/6JNarl mice
作者: 沈婷婷
Shen, Ting-Ting
關鍵字: olanzapine
奧氮平
resveratrol
白藜蘆醇
出版社: 獸醫學系暨研究所
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摘要: 非典型抗精神藥物(如:金菩薩)為精神分裂症病患帶來多種福利,包括:改善負向情緒徵狀、低錐體外症狀發病率。然而在臨床研究上顯示服用非典型抗精神藥的病患出現代謝症候群副作用,對於所引發副作用的機制仍未了解。近年來許多研究證實白藜蘆醇具有保護心血管及抗發炎的特性。本研究為建立金菩薩誘導肥胖之C57BL/6JNarl動物模式,並利用白藜蘆醇(resveratrol)特性來探討是否能改善金菩薩所引發的代謝副作用。本研究初步結果顯示:服用金菩薩的確會增加食慾(P<0.01)而造成肥胖(P<0.05),並且也會出現高血糖(P<0.05)及高血脂(P<0.001)代謝異常的情形,雖然血清中胰島素和HOMA-IR並未達到統計學上的顯著標準,但有上升趨勢。另外透過光學顯微鏡觀察到經過H&E染色脂肪細胞,金菩薩會引起脂肪細胞變大的趨勢。透過西方點墨法,我們發現到金菩薩會造成肝臟中的AMPK活性降低(P=0.06);然而結合白藜蘆醇補充之後,增加肝中AMPK活性(P<0.05),改善代謝異常的情形,降低血脂(P<0.001)以及促進胰島素的敏感度(P<0.05),且達到有效抑制金菩薩所引起的肥胖(P<0.05)。本研究顯示白藜蘆醇可以活化AMPK活性,而改善金菩薩誘導的肥胖及異常代謝情形。在未來或可應用於臨床上的精神病患來改善代謝異常副作用。
Atypical antipsychotics, such as Olanzapine (Zyprexa&reg;) offer several notable benefits to treat schizophrenia, including greater improvement in negative symptoms and a lower risk of extrapyramidal sysmptoms (ESP). However a major downfall to their use is metabolic side-effects particularly weight gain/obesity, which occurs by unknown mechanisms. Recent studies have demonstrated that resveratrol has cardioprotective abilities and anti-inflammatory effect. Thus, this study was designed to investigate the inhibitive effects of resveratrol on Olanzapine-induced metabolic side effects by using C57BL/6JNarl mice model. In our preliminary studies, olanzapine administration led to remarkable overweight (p<0.05) and hyperphagia (p<0.05). Moreover, olanzapine-induced obesity mice appeared hyperglycemia (p<0.05) and dyslipidemia (p<0.001). Morphometric analysis of olanzapine-treated mice adipocytes in abdominal fat pads by H&E staining showed a large in fat cell size as compared to the control group. Importantly, the combine of reveratrol supplement could appeared that the best inhibitory effect on weight gain (p<0.01), high blood glucose (p<0.05), dyslipidemia (p<0.001) and improve insulin sensitively (p<0.05). By using western blot analysis, we found that olanzapine combined reveratrol supplement group have significance increase of AMPK expression in liver (p<0.05). In particular, long-term supplement of resveratrol could activate the AMPK activity and could improve the olanzapine-induced abnormal glucose and lipid metabolisms. Overall, this study provides some information into the basis of olanzapine-induced metabolic side effects.
URI: http://hdl.handle.net/11455/12844
其他識別: U0005-0708201117405500
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-0708201117405500
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