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  • 學位論文

利用小鼠模式探討中草藥對代謝症候群危險因子之影響

The Effects of Chinese Herbal Medicine on Reducing the Risk Factors of Metabolic Syndrome in a Mouse Model

指導教授 : 林淑容
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摘要


代謝症候群是一種包含肥胖、血壓偏高、血糖偏高以及血脂異常等多項危險因子綜合表現的臨床徵候,伴隨著這些危險因子的增加,罹患心血管疾病、糖尿病和高血壓的機率也相對提升。根據行政院衛生署 2011 年公佈的國人十大死因中,心臟疾病、腦血管疾病、糖尿病、腎相關疾病以及高血壓性疾病等多項與代謝症候群相關的疾病,其總死亡率遠高於排名第一的惡性腫瘤。因此,本研究利用 C57BL/6 純種品系小鼠,藉由注射Streptozocin (STZ) 並餵食高脂質飼料,建立代謝症候群小鼠模式後,再經由口服餵食三黃瀉心湯,以評估三黃瀉心湯是否可以有效改善代謝症候群之危險因子,並探討三黃瀉心湯改善代謝症候群之相關機制。實驗結果發現,小鼠注射 STZ 並餵食高脂質飼料八週後,可成功建立具有高血糖、葡萄糖不耐症、高膽固醇血症、脂肪肝以及發炎反應等多項代謝症候群危險因子之小鼠動物模式;而每天口服餵食三黃瀉心湯十一週後,結果發現,餵食三黃瀉心湯雖然無法有效改善小鼠之高血糖及高膽固醇血症,但可降低小鼠肝臟重量及肝臟內三酸甘油酯濃度,減低血漿中 E-selectin 濃度,並提升脂肪組織 PPARγ2、肝臟 PPARα、及降低肝臟 IL-6、TNF-α、IL-1β、COX-2 和 mPGES1 等發炎或調節因子的 mRNA 表現。因此,總結本研究結果,C57BL/6 純種品系小鼠注射 STZ 且餵食高脂質飼料,可成功建立具有高血糖、葡萄糖不耐症、高膽固醇血症、脂肪肝以及發炎反應等多項代謝症候群危險因子之小鼠動物模式;而口服三黃瀉心湯,雖無法有效改善小鼠高血糖及高膽固醇血脂症之徵候,但可改善脂肪肝及肝臟之脂質代謝、增加脂肪組織代謝作用,並減緩小鼠發炎反應,可作為改善發炎反應及脂質代謝之藥物。

並列摘要


Metabolic syndrome is characterized by obesity, hypertension, hyperglycemia and dyslipidemia as well as a cluster of risk factors. Along with these risk factors rising, the probability of suffering from cardiovascular disease, diabetes and hypertension would be increased. In Taiwan, the total mortality of metabolic-syndrome-related diseases including cardiovascular diseases, cerebrovascular diseases, diabetes, kidney diseases, and hypertension-related diseases is higher than cancers. In order to establish a mouse model with the risk factors of metabolic syndrome, C57BL/6 male mice were injected with streptozocin (STZ) and fed with high-fat diet for eight weeks. After that, San-Huang-Xie- Xin-Tang (SHXT) was orally administrated daily for 11 weeks to evaluate whether the SHXT could ameliorate metabolic syndrome and to study its molecular mechanisms. The results showed that a mouse model with hyperglycemia, glucose intolerance, hypercholesterolemia, fatty liver and intensive inflammation was successfully established. Although SHXT failed to improve hyperglycemia and hyper- cholesterolemia, it reduced liver weight and triacylglyceride, and plasma E-seletctin concentration, increased the expression of adipose PPARγ2, and hepatic PPARα, decreased hepatic IL-6, TNF-α, IL-1β, COX-2 and mPGES1 mRNA. In conclusion, C57BL/6 mice injected with STZ and fed with high-fat diet for 8 weeks is a good model for evaluating the treatment for improving hyperglycemia, glucose intolerance, hypercholesterolemia, fatty liver and inflammation. Although oral admi- nistration of SHXT could not improve some of the metabolic risk factors effectively, it could modulate fatty liver, adipose and hepatic lipid metabolism, and inflammation.

參考文獻


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