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Please use this identifier to cite or link to this item: http://ntour.ntou.edu.tw:8080/ir/handle/987654321/30228

Title: Adiponectin 改善clozapine引發的脂質堆積及發炎反應,但不影響胰島素阻抗性
Adiponectin improves clozapine-induced lipid accumulation and inflammation without affecting insulin resistance
Authors: 蔡宜倫
Contributors: NTOU:Institute of Bioscience and Biotechnology
國立臺灣海洋大學:生物科技研究所
Keywords: clozapine;adiponectin
Date: 2011
Issue Date: 2011-11-25T07:36:30Z
Abstract: 第二代抗精神病藥物易造成體重增加,使精神病患易罹患糖尿病、心血管疾病及其它的併發症包含脂肪肝。Clozapine引發的體重增加在第二代抗精神病藥物中最為顯著,本實驗室先前實驗在老鼠3T3L1脂肪細胞中,證明clozapine會抑制adiponectin的分泌,由於adiponectin是完全由脂肪細胞所分泌之細胞素,可透過paracrine作用於肝臟細胞上,且具抗發炎及改善胰島素阻抗性;且先前clozapine也證實會引發肝臟細胞發炎及胰島素阻抗性,故本論文針對(1) clozapine是否會造成人類肝臟細胞累積脂質;(2) adiponectin是否可抑制clozapine造成人類肝臟細胞的發炎反應及胰島素阻抗性;進行相關探討。本論文初步結果顯示clozapine處理人類肝癌細胞株HepG2,以螢光染劑標定脂質,再以流式細胞儀進行測定,隨著時間脂質的累積增加。脂質合成途徑(lipogenesis)的脂質合成酶(fatty acid synthase; FASN)量增加。而以real-time PCR偵測clozapine影響細胞中adipoR1及adipoR2 mRNA的表現,也發現clozapine可抑制adipoR1及adipoR2 mRNA的表現。在 HepG2細胞大量表現adiponectin蛋白,發現確實在adiponectin的存在下,可抑制clozapine造成的脂質累積。另外,adiponectin的確可以降低clozapine所造成的NF-κB之發炎反應但adiponectin對clozapine引發的胰島素阻抗性卻無影響。綜合這些結果,未來研究方向將進一步釐清adiponectin為何無法改善clozapine誘發的胰島素阻抗性進行相關探討。
Atypical antipsychotic drugs (AAPDs) may cause side effects including weight gain, diabetes, and other cardiovascular diseases such as fatty liver. Clozapine-induced weight gain is most significant in cases of AAPDs. Our previous data showed that clozapine could inhibit adiponectin secretion in mouse 3T3L1 adipocytes. Adiponectin, a cytokine secreted by adipocytes, can act on hepatocyte by means of paracrine. Adiponectin has anti-inflammation and insulin-sensitizing properties. We have demonstrated that clozapine could induce liver inflammation and insulin resistance in hepatocyte. In this study, we sought to elucidate whether clozapine could cause lipid accumulation as well as whether adiponectin would inhibit clozapine-induced inflammation and insulin resistance in human hepatocyte. Lipid was first labeled with fluorescent dye and its accumulation was analyzed by flow cytometry. This result indicated a time-dependent lipid accumulation in clozapine-treated HepG2 cells. The level of fatty acid synthase (FASN) of lipogenesis pathway was also increased. We investigated adipoR1 and adipoR2 mRNA expression by real-time PCR, and both adipoR1 and adipoR2 mRNA expressions were inhibited by clozapine. In addition, adiponectin indeed inhibited lipid accumulation when adiponectin was overexpressed in HepG2 cells. Moreover, the result showed that adiponectin significantly improved the inflammation induced by NF-κB but exerted no effect on insulin resistance induced by clozapine. In the future, we will further investigate the inability of adiponectin to improve insulin resistance induced by clozapine.
URI: http://ethesys.lib.ntou.edu.tw/cdrfb3/record/#G0M98360026
http://ntour.ntou.edu.tw/handle/987654321/30228
Appears in Collections:[生命科學暨生物科技學系] 博碩士論文

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