南京工业大学硕士学位论文小麦α-淀粉酶抑制剂的药理药效研究姓名：陈宁申请学位级别：硕士专业：生物化工指导教师：陈国广;张琪20060601摘要目的：为了进一步的研究和了解由我校生化中心采用专利技术从小麦粉中分离纯化的α-淀粉酶抑制剂的化学成分和作用机理，以便更全面的开发和利用这种资源，本课题进行了小麦α-淀粉酶抑制剂的降糖﹑调脂和减肥功能的作用研究，并且系统研究了α-淀粉酶抑制剂的作用机理，从而为今后把α-淀粉酶抑制剂开发成保健品或药品提供依据和参考。
方法：（1）α-淀粉酶抑制剂降血糖作用的实验研究：四氧嘧啶性糖尿病小鼠灌胃给予α-淀粉酶抑制剂45 mg·kg-1，测定其淀粉耐量和糖耐量；四氧嘧啶性糖尿病小鼠灌胃给予α-淀粉酶抑制剂（5、15、45 mg·kg-1），连续21d后，测定血糖值和小肠内二糖酶活性。
（2）α-淀粉酶抑制剂的调脂作用：采用不同剂量α-淀粉酶抑制剂（5、15、45 mg·kg-1）分别对高脂血症大鼠进行预防性给药和治疗性给药，给药结束后测定其血液中的TC﹑TG﹑HDL－C和LDL－C含量，称取大鼠肝脏并称肝重，并测定肝脏TC、TG含量，同时对肝脏进行常规切片、HE染色后在光镜下观察组织形态改变。
（3）α-淀粉酶抑制剂的减肥作用：以肥胖模型大鼠为研究对象，通过对肥胖大鼠灌胃不同剂量的α-淀粉酶抑制剂（5、15、45 mg·kg-1），连续28d，动态监测大鼠体重变化，并测定lee指数和脂肪湿重。
结果：（1）α-淀粉酶抑制剂能够增加小鼠的淀粉耐量而对其葡萄糖耐量没有影响；糖尿病小鼠灌服α-淀粉酶抑制剂45 mg·kg-1和15 mg·kg-1后，血糖值均明显低于模型对照组，结果有显著性差异；α-淀粉酶抑制剂能有效抑制小鼠小肠内各部分的麦芽糖酶和蔗糖酶活性，尤其是对前段小肠内二糖酶的活性抑制较强。
（2）α-淀粉酶抑制剂在对高脂血症大鼠进行预防性给药时可以明显抑制TC、TG、LDL-C及AI的升高，抑制HDL-C的降低，特别是高剂量组，而且可以降低肝脂含量，减轻肝脏脂肪病变。
治疗性给药时α-淀粉酶抑制剂高剂量组和阳性药组的数据与模型组相比有显著性差异，而其他剂量组数据与模型组相比没有显著性差异。
（3）给药28d后，各α-淀粉酶抑制剂给药组与模型组相比较，lee指数和脂肪湿重都有不同程度的降低，其中α-淀粉酶抑制剂高剂量组变化明显，与阳性药给药组相比结果差异不大。
结论：（1）α-淀粉酶抑制剂能抑制与淀粉吸收相关的胃肠道内多种淀粉酶的活性，使食物中大量的碳水化合物主要在小肠的末端被吸收，从而延长了食物在肠道中的消化时间，导致机体吸收葡萄糖的速率下降，因而可有效改善了小鼠进食后血糖波动情况，使葡萄糖耐量曲线变得平缓，保持血糖餐后稳定在正常水平或接近正常水平范围内，因此起到降低血糖及治疗糖尿病的作用。
（2）α-淀粉酶抑制剂对高脂血症能够有较好的预防作用和一定的治疗效果。
（3）α-淀粉酶抑制剂对由营养饲料喂养成型的肥胖大鼠的肥胖症治疗疗效确切，α-淀粉酶抑制剂可减少糖向脂肪转化，增加脂肪消耗以减轻体重。
关键词：α-淀粉酶抑制剂 starch blocker 降血糖二糖酶减肥降血脂糖耐量高脂血症ABSTRACTObjective: In order to study the action of α-amylase inhibition which were separated and purified from wheat by biochemical center. In this topic, we study the action of α-amylase inhibition in hypoglycemic、weight-reducing 、hyperlipemia and its mechanism. It provides references for α-amylase inhibition developed as a new health product or drug.Methods:(1)The hypoglycemic action of α-amylase inhibition: Diabetes mice were treated with α-amylase inhibition(5、15、45 mg·kg-1) by gastric perfusion for 21d and their BG level and disaccharidase activity were measured. Diabetes mice were treated with AI 45mg/kg by gastric perfusion and their starch and sugar tolerance were measured. Disaccharidase activity in various segments of mice’ small intestine was determined by Dahlqvist method.(2) The hyperlipemia action of α-amylase inhibition: Use different dose of α-amylase inhibition treat the hemorheology rat in the prevention study and therapeutic study. The concentration of TC、TG、HDL-C、LDL-C in serum and TC、TG in liver was determined, and the hemorheology and pathological changes of liver and artery were also observed.(3) The weight-reducing action of α-amylase inhibition: Fat rat were treated with α-amylase inhibition(5、15、45 mg·kg-1) by gastric perfusion for 28d and their weight、lees and fat’s weight were measured.Result:(1) α-amylase inhibition can increase the starch tolerance of diabetes mice but not change the sugar tolerance. The BG level in diabetes mice received 15 and 45 mg·kg-1 of α-amylase inhibition for 21d was significantly decreased in comparison with the model control group. α-amylase inhibition also could inhibit the disaccharidase activity in various segments of mice small intestine.(2) In the prevention study, α-amylase inhibitor of the middle and high doses can markedly decrease the concentration of TC、TG、LDL-C in serum, TC、TG in liver,increase the concentration of HDL-C, α-amylase inhibitor of the high doses can also improve pathological changes of liver. In the therapeutic study, the lipid levels of high dose group and positive group have significant differences compared to model group. There are no significant differences between middle dose group and low dose group.(3) After 28d, the lee’s and fat weight of each α-amylase inhibition groups have significant differences compared to model group. The result of the high dose group approximates the positive group.Conclusion:(1) α-amylase inhibition can inhibit several amylase activity in gastrointestinal. α-amylase inhibition delayed carbohydrate absorption, increased carbohydrate delivery to the ileum, and delayed gastric emptying and reduced postprandial plasma concentrations of glucose in mice, keep the BG level in the normal level. So α-amylase inhibition could cure and provide diabetes.(2) α-amylase inhibitor can prevent hyperlipemia and have effects on formed hyperlipemia.(3) α-amylase inhibitor can obviously lose weight, it can reduce the glucose transform to fat and increase the consume of fat.KEYWORDS：α-amylase inhibitor starch blocker hypoglycemic weight-reducing hypolipemic disaccharidase starch tolerance缩略词表简写英文全称中文全称AI α-amylase inhibitor α-淀粉酶抑制剂TC total cholesterol 总胆固醇TG triglyceride 甘油三酯HDL-C high density lipoprotein cholesterol 高密度脂蛋白-胆固醇LDL-C low density lipoprotein cholesterol 低密度脂蛋白-胆固醇ig intragastric 灌胃注射南京工业大学学位论文独创性声明及使用授权的声明一、学位论文独创性声明本人声明所呈交的学位论文是我个人在导师指导下进行的研究工作及取得的研究成果。