中文摘要
本實驗的目的為使用穿心蓮素來解明穿心蓮的降糖機轉，藉此開發新的糖尿病治療用藥。初步發現，不論是胰島素缺乏的大白鼠(IDDM)或正常大白鼠身上，穿心蓮素都能以一個劑量相關的方式降低血糖。同時，在葡萄糖挑戰試驗中，穿心蓮素會增加週邊組織對葡萄糖的利用率。此外，穿心蓮素也能刺激IDDM大白鼠骨骼肌對葡萄糖的吸回作用，並促進肝臟的肝糖合成。由此可知，胰島素缺乏時，穿心蓮素也具有降糖能力。文獻指出，在胰島素缺乏的大白鼠身上，藉由投與藥物刺激腎上腺分泌b-endorphin，它能活化周邊組織的嗎啡m型受體，進而產生降血糖作用。因此，使用enzyme-linked immunosorbent assay技術檢測IDDM大白鼠血中b-endorphin的濃度。發現穿心蓮素會以劑量相關的方式增加血中腦內啡的含量；這項作用會被嗎啡μ型受體阻斷劑的naloxone或naloxonazine依劑量相關的型式阻斷穿心蓮素的降血糖效果。另外，在嗎啡μ型受體剔除的糖尿病小鼠，靜脈注射給予能產生降血糖濃度的穿心蓮素，卻看不到原先的降血糖作用；顯示穿心蓮素的降糖作用與嗎啡μ型受體有關。由此可知，在胰島素缺乏的糖尿病大白鼠，穿心蓮素會產生降血糖的作用，主要是透過體內b-endorphin作用，活化週邊組織的嗎啡μ型受體，增加葡萄糖利用以及抑制糖質新生作用來產生降糖作用。

In the present study, the antihyperglycemic action and possible mechanism of andrographolide were investigated. A dose-dependent lowering of plasma glucose was observed both in the streptozotocin (STZ)-induced diabetic rat and Wistar rats, after oral treatment (P.O.) of andrographolide. Andrographolide at an effective dose significantly attenuated the increase of plasma glucose induced by intravenous glucose challenge test in Wistar rats. Stimulatory effects of andrographolide on the glucose uptake and glycogen synthesis were also obtained in soleus muscles and hepatocytes isolated from STZ-diabetic rats indicating an increase of glucose utilization by androgrpholide in a way not dependent on insulin. In our previous study, we found that b-endorphin isresponsible for production of hypoglycemic effect is STZ-diabetic rats. Increase of plasma b-endorphin in STZ-diabetic rats seems important for compensation of hyperglycemia. Andrographolide at the effective dose increased the plasma b-endorphin level in STZ-diabetic rats. The plasma glucose lowering effect of andrographolide was also abolished by naloxone or naloxonazine. Plasma glucose lowering action of andrographolide at the dose effective in diabetic rats was disappeared in opioid m-receptors knockout mice. The obtained results suggest that the release of b-endorphin seems responsible for the lowering of plasma glucose in STZ-diabetic rats by andrographolide. Activation of opioid m-receptors by b-endorphin can increase the utilization of glucose and/or decrease hepatic gluconeogenesis to lower plasma glucose in diabetic rats lacking insulin.

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