中西藥併用之安全性探索

許游章
中國醫藥大學
根據衛生署的統計，糖尿病居十大死因的第五位，且近幾年來快速成長，並以非胰島素依賴型糖尿病(NIDDM; type II)為主，約佔罹患率的95%左右。目前雖有胰島素注射劑及口服降血糖藥物，但在臨床上之使用仍未達理想。已有文獻指出糖尿病之高血糖會引發身體的自由基過度增加，而導致諸多糖尿病的慢性合併症。氧化壓力增加亦對許多細胞功能造成損害，並因體內抗氧化防禦系統能力的降低使得糖尿病患者體內的氧化壓力、蛋白質糖化均較正常人嚴重，再加上脂質代謝不良，是引發糖尿病併發症的主因。但是，糖尿病患者若血糖控制良好，可使患者體內的氧化壓力及蛋白質糖化作用降低。西藥Glipizide屬於第二代 Sulfonylurea的降血糖藥物，適用於非胰島素依賴型糖尿病，其作用為刺激胰臟分泌胰島素，但是副作用會造成低血糖、發燒、喉嚨痛，皮膚疹，黃疸症狀等症狀。我國傳統醫學研究指出槐花含有Rutin 和 Quercetin，中醫常用於涼血、止血，現代藥理研究指出其可用於治療腦血管相關疾病及防止DNA 受外來化學物質的破壞，並具有血管舒張、清除自由基、降低血清膽固醇、降血壓、降血脂、抗發炎及抗癌等作用。因此本計畫以常用之降血糖西藥Glipizide併用藥用植物槐花進行降血糖及氧化壓力探討，並期望Glipizide使用劑量減少，減少Glipizide之副作用，以尋得先導中西藥併用藥物以供醫學研究依據。另一方面，糖尿病患者可能會同時服用Glipizide及槐花，是否引發交互作用值得探討。本計畫以大鼠為動物模式，評估中西藥交互作用發生機會與其機制。以Nicotinamide (180 mg/kg, ip)及STZ (streptozotocin, 65 mg/kg, iv) 誘發糖尿病，當血糖達到200 mg/dL，判定為糖尿病老鼠。實驗分成五組，一組為空白組，不誘發糖尿病，其餘四組則誘發糖尿病，一組給予標準配方飲食，做為控制組，第二組則添加槐花(2 g/kg, bid)，第三組則給與口服降血糖藥(Glipizide, 1 mg/kg)，第四組則給予槐花及Glipizide。實驗期四週，實驗期間採取血液分析，進行口服葡萄糖耐受度測試(OGTT)，並於實驗期結束犧牲老鼠取血液分析，測定血中之葡萄糖及胰島素含量做為指標，氧化壓力以抗氧化防禦系統中的抗氧化酵素活性做為參考依據。初步研究結果發現，糖尿病鼠之體重、飲水量與尿量均較控制組顯著增加。本研究目的將釐清Glipizide及槐花併用之相關機制，探索其實證，期能規劃研究成果，以利國人用藥安全，並進一步期望能尋找可降低口服醬血糖藥物之中草藥。
關鍵字：槐花；超氧歧化；糖尿病鼠；交互作用；藥物動力學；中草藥

Exploration of the safety of concurrent use of herbs with western medicine

Hseu, You Cheng
China Medical University
Sophorae flos, a Chinese herb, contains aboundant flavanol aglycon including rutin and quercetin. There are reports that indicated used for treatment of cerebral vessels associated disease and prevention of DNA dystruction by external chemicals. Oxidative stress, glycation and lipid metabolism have been proposed to be linked and be increasing to tissue damage and the development of pathophysiology in diabetic patients. The purpose of this projected is evaluated the effects of Sophorae flos on oxidative status, insulin and blood glucose in diabetic rats. Diabetic rats were induced by injecting with nicotinamide (NTA; 230 mg/kg, ip) and 65 mg/kg/day streptozotocin (STZ) in citrate buffer 2 days, continuously. While the blood sugar over 200 mg/dL was defined as the diabetic rats, and then feeding the different experimental diets. Male adult Wistar rats (b.w eq. 125-150 g) were divided into five groups: Blank group was injected with saline and citric buffer, the others groups were injected with NTA and STZ, feeding with standard diet, with or without Sophorae flos and/or Glipizide, respectivelly. Bloods samples were colledted every three days and OGTT was examed on 25th day. Four weeks later, the diabetic rats were sacrificed and sampled. The indicator of oxidative status were individually evaluated the activity of antioxidant enzyme (SOD and GPX).
關鍵字：Sophorae flos；super oxygen dimutase；diabetic rats；drug interaction；pharmacokinetic；herb