胰安肽口服改善糖脂代谢作用研究

 目的 探讨新生物活性肽胰安肽口服对糖尿病小鼠血糖、血脂代谢的影响及用药安全性。方法 采用一次大剂量腹腔注射链脲佐菌素(STZ， streptozotocin， 100 mg·kg-1）并用高脂饲料喂养建立糖尿病伴高血脂小鼠模型。隔日灌胃（ig，intragastrically）给予胰安肽（15 mg·kg-1），并设二甲双胍作为阳性对照。治疗期间进行血糖 (BG) 检测，口服糖耐量测试（OGTT）。实验结束后测定血清胰岛素，血清总胆固醇（TC）和甘油三酯（TG）水平。同时测定肝、脾和肾等重要脏器指数及药物的体外急性毒性。结果 给药期间，胰安肽给药组血糖水平显著低于模型组，胰安肽组口服糖耐量明显高于模型组（P<0.01）。胰安肽可显著降低高血糖、高血脂小鼠血清甘油三酯水平（P<0.05），并改善总胆固醇水平。各组小鼠血清胰岛素水平无显著差异（P>0.05）。连续给药过程中，胰安肽对各重要脏器无损害。体外研究显示，胰安肽对HepG2细胞无抑制作用，未能测出胰安肽的LD₅₀ 。结论 口服胰安肽可改善糖尿病小鼠的血糖及血脂紊乱，长期给药较为安全可靠，可开发为防治糖尿病、高血脂等代谢综合征的新药。

Effect of Aglycin on Blood Glucose and Lipid Metabolism Via Oral Administration

OBJECTIVE To investigate effects of the new bioactive peptide， aglycin， on blood glucose and lipid metabolism in diabetic mice， and evaluate its safety. METHODS The murine diabetic model was induced by a single intraperitoneal (ip) injection of STZ (streptozotocin， 100 mg·kg-1) in mice which was fed with a high fat diet. The diabetic mice were orally administered 15 mg·kg-1 aglycin once every two days for 40 d. And metformin-treated diabetic mice recevied 100 mg·kg-1 metformin， whereas diabetic and normal control mice were given 0.9% NaCl ig instead. Blood glucose was determined during the treatment and oral glucose tolerance tests were performed after the last administration. The total cholesterol， triglyceride and insulin in serum were determined after treatment. Furthermore， the tissue index and in vitro acute toxicity were determined. RESULTS After 40 d of treatment， glucose concentration was (7.45±0.14） mmol·L-1 in the aglycin-treated animals compared with （11.10±0.89） mmol·L-1 （P<0.01 ） in the saline-treated animals. Aglycin-treated diabetic mice had a lower maximum blood glucose at 0.5 h and achieved a decreased glucose AUC (P<0.05) in the OGTT study. It was demonstrated that aglycin significantly decreased total cholesterol and triglyceride in serum as well. However， serum insulin level was not significantly different among diabetic mice. Vital organs indexes showed no change and damage after 40 d aglycin treatment. Aglycin had no inhibitory effect on HepG2 cells proliferation and therefore LD₅₀ value was unable to be calculated. CONCLUSION Aglycin has a beneficial effect on blood glucose and lipid control， and is safety enough as a long-term oral agent for diabetes. It could therefore be developed as a potential oral agent for prevention and treatment of hyperlgycemia， hyperlipidemia and metabolic syndrome， et al.