蛇床子素改善新陳代謝症候群之研究

Study of Osthole on the improvement of metabolic syndrome in mice

林秀敏(Hsiu-Ming Lin)

指導教授 ： 梁有志

臺北醫學大學/醫學院/醫學科學研究所/碩士(2010年)

https://doi.org/10.6831/TMU.2010.00243

摘要

因為先前本研究室觀察到，由中草藥所純化出來的疏水性化學物質蛇床子素 (Osthole)，可以誘導糖尿病鼠(db/db mice)之 HepG2 肝癌細胞表現 PPARα 標的基因增加，並可經由活化 AMPK 而降低血糖值的表現，進而在本研究中進一步探討蛇床子素 Osthole 對改善代謝症候群的關聯性。

為了要多了解蛇床子素 Osthole 在不同的糖尿病模式下，是否也具有相同的降血糖功能，因此設計非基因鼠的動物模式來研究。先利用飲食誘導肥胖( diet induced obesity,DIO )之 C57BL/6J 及 ICR 動物模式，模擬人類因肥胖而造成高血脂及高血糖演化過程，經由高脂飼養誘導正常雄性 C57BL/6J 及 ICR 小鼠，使具中度肥胖及第2型糖尿病與葡萄糖耐受性不良等症狀，來探討代謝症候群的變化。

DIO 組以 60% 高脂錠劑飼料餵食，誘發產生與代謝症候群相似之高血脂及高血糖之模式。第31週犧牲小鼠，檢測血糖 Glucose、三酸甘油脂 Triglyceride及膽固醇 Cholesterol等生化值，肝臟秤重並做成組織切片染色，胰臟組織切片做免疫組織化學染色，觀察胰島素的分泌及巨噬細胞在白色脂肪組織上的浸潤情形，以了解 osthole 對新陳代謝症候群的醣類與脂質代謝的影響。

接著，單次腹腔注射 100 mg/dl STZ ( streptozotocin ) ICR 雄性 ICR 鼠，經過四週誘導後，暫時破壞小鼠的胰臟β細胞，產生高血糖症，使小鼠模擬第2型糖尿病的情況，再以不同osthole濃度( 30 mg/kg、100 mg/kg )灌食4週及腹腔注射( 100 mg/kg )方式，分別給予 ICR 小鼠5週，之後再與未施打 STZ 的正常對照組做比較。觀察不同濃度的蛇床子素 Osthole 是否能減緩 STZ 對胰島細胞的傷害，而具有抗新陳代謝症候群的醣類與脂質代謝作用。

本研究最後發現，在實驗A、B以高脂飼養小鼠的方式，成功誘導小鼠成為具新陳代謝症狀的肥胖鼠，而低脂 + 10 mg/kg osthole的飼養組，Osthole可以降血糖及血脂。在高脂飼養誘導肥胖小鼠的實驗2部份證實高劑量蛇床子素可以降低血糖值，在注射鏈球菌素 STZ 誘導糖尿病實驗 D 部份更進一步證實，以高劑量100 mg/kg osthole以灌食方式，比腹腔注射較具有降血糖的作用，但是對於降血脂的功能則不顯著。基本上osthole具有第二型糖尿病藥物開發潛力。

關鍵字

Osthole ； 代謝症候群 ； 肥胖

並列摘要

Osthole, a coumarin compound, is isolated from the dried fruits of Cnidium Monnieri (Umbelliferae) that has been used as a Chinese herb medicine. Recent our studies have found that osthole was able to decrease blood glucose level in db/db and ob/ob diabetic mice. The hypoglycemic activity of osthole might be associated with the activation of PPAR and AMPK in cells. Other studies indicated that osthole also had a hypolipidemic activity in fat- and milk-induced dyslipidemic animals. To understand whether osthole can improve the metabolic syndrome including hyperlipidemia and hyperglycemia, diet-induced obesity (DIO) mice and streptozotocin (STZ)-induced diabetic mice were used to evaluate the biological function of osthole.
The results showed that high-fat diet indeed induced metabolic syndrome such as obesity, high level of blood cholesterol and glucose, and steatosis in DIO mice. However, there was no change in blood triglyceride level between control and DIO mice. Because the mice wouldn’t like to take the predesignated diet (high-fat diet containing 1% osthole), we did not known whether osthole can improve the metabolic syndrome in DIO mice.
Next, we examine whether osthole can decrease blood glucose level in STZ-induced diabetic mice. After single i.p. injection of 100 mg/kg STZ, osthole was gave by either oral gavage or i.p. injection for 5 weeks. In the STZ mice, the blood glucose levels rose markedly from 5 week after STZ administration and the high glucose levels were thereafter decreased until the end. Oral osthole treatment but not i.p. treatment resulted in a significant decrease of fasting blood glucose level at weeks 5-8. On the other hand, osthole did not change the blood levels of cholesterol and triglyceride in both oral and i.p. treatment mice. These results suggest that osthole has potential value as an antidiabetic agent for the treatment diabetes.

並列關鍵字

Osthole ； Metabolic syndrome ； Obesity

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