【作者】 张阳；

【导师】 黄自强；

【作者基本信息】 福建医科大学 ， 药理学， 2002， 硕士

【摘要】 一、糖脂平对正常和实验性糖尿病小鼠血糖的影响。以糖脂平3.5、7.0和14.0g／kg给小鼠灌胃，1／d×5。结果显示：该药能维持正常小鼠空腹血糖的稳定性，对葡萄糖、肾上腺素、四氧嘧啶所致的小鼠高血糖均有明显的抑制作用。此外，该药给小鼠灌胃，其最大耐受量为68.75g／kg，相当于成人日用量的395倍，显示该药毒性极小，口服安全。 二、糖脂平对实验性NIDDM模型大鼠糖脂代谢、胰岛功能的影响。SD大鼠在高热量饲料(含10％猪油、10％花生油，15％炼乳)喂养一月的基础上，以链脲佐菌素33mg／kg尾静脉注射制备实验性肥胖及糖尿病模型鼠，同时给予糖脂平生药3.5、14.0g／kg灌胃，1／d×36d。结果显示：糖脂平能明显降低模型鼠的体重增长率，明显抑制模型鼠血清甘油三酯的升高。对模型鼠增高的空腹血糖有明显降低作用，且又能抑制糖负荷1h、3h后血糖的升高。对模型鼠呈现的高胰岛素和高胰高血糖素血症有下降作用(高剂量组与模型组比较，血清胰岛素下降15.29％，P〉0.05；血清胰高血糖素下降21.81％，P<0.05)，说明糖脂平台能抑制模型鼠的胰高血糖素分泌、体重增长，改善糖脂代谢紊乱，进而减轻模型鼠的胰岛素抵抗。 三、糖脂平对实验性糖尿病大鼠坐骨神经和晶体糖醇代谢的影响。SD大鼠尾静脉注射四氧嘧啶40mg／kg制成四氧嘧啶糖尿病模型鼠，用糖脂平生药4.7、14.0g／kg灌胃，1／d×30。结果：糖脂平有效地降低糖尿病大鼠血糖的含量，有效地降低其坐骨神经和晶体中葡萄糖的含量，对坐骨神经和晶体中山梨醇的含量有降低作用(高剂量组与模型组相比，分别下降23.80％和26.42％，0.05〈P〈0.1)，对肌醇含量无明显改变。糖脂平治疗30d后坐骨神经电镜观察显示，糖脂平有改善大鼠坐骨神经脱髓鞘、轴索变性、线粒体肿胀等病理变化。提示糖脂平对糖尿病大鼠坐骨神经病变有一定防治效果，其作用途径与其降血糖以及改善神经和晶体组织内糖醇代谢有关。 四、糖脂平对四氧啼陡糖尿病模型鼠肾脏病变及相关状况的影响以及糖B秤的降糖机制。结果表明：高剂量糖脂平可明显改善模型鼠症状，明显降低糖尿病血糖、尿素氮、尿蛋白排泄率，明显降低糖尿病血清胆固醇和甘油三酯水平。对糖尿病早期的肾脏肥大、肾小髓脑－，提撇脚一其栅、降脂、改善黝能、改善肾血流动力学的作用，对糖尿病大鼠肾脏具有一定的保护作用。此外，糖脂平可明显降低徽鼠糖化血红蛋白的作用，提稠剧秤可能具有蛋白质非娜化抑制剂样作用。撇平对糖尿病模型鼠显著降低的空腹血清胰岛素略有增加，但差异无显著意义。结合胰腺病理检查推断出糖脂平的降糖机理存在胰外作用。其作用机理可ggffi41；t于双肌类药物如降糖灵等，一方面抑制肠蹦葡萄糖的吸收，另一方面直接影响糖代谢。更多还原

【Abstract】 1. The effect of herba TZP on blood sugar in normal and experimental diabetic mice. The blood glucose level in mice was monitored after ig. TZP at doses of 3.5, 7.0 and 14.0g/kg, l/dX5. which indicates that TZP can keep the stability of empty-stomach blood glucose in normal mice and significantly decrease the blood glucose of diabetic mice caused by adrenalin,glucose and alloxan. Besides, the largest enduring dose of mice daily is 68.75g/kg after ig.TZP, which is 395 times more than adult The above explains that TZP contains little toxin.2.The effect of herba TZP on glucolipide metabolism and function of islets of pancreas in experimental NIDDM diabetes mellitus. SD rats were fed with a high quantity of heat diet enriched with peanut oil(10%,w/w), triglyceride (10%,w/w) and condensed milk (15%,w/w). After one month on the diet, STREPTOZOTOCIN(stz, 33mg/kg) was injected into tail-vein to develop experimental fat and diabetic rats. Meanwhile, the rat models were treated with TZP at dosed of 3.5, 14.0g/kg , l/dX36. Results show: TZP can clearly decrease the weight-growth rate and the level of serum triglyceride in the rat models, and reduce the empty-stomach blood glucose rising and inhibit blood glucose growing caused by glucose loading test Ih, 3h. Besides, TZP can cause hyperinsulin and hyperglycemic trend to decreasing [compared with negative control groups, the serum insulin and glucagon in the groups of higher dose of TZP decreased by 15.29% (PXX05) and 21.81% (PO.05) separately), which indicates TZP can inhibit secretion of serum glucagon and growth of weight, improve disturbance of glucolipidemetabolism so that it can lower insulin resistance in the rat models.’3.The effect of TZP on polyols in sciatic nerve and lens of diabetic rats. Alloxan 40mg/kg was injected into SD rat’ tail vein to develop alloxan diabetic rat models, which were treated with TZP at doses 4.7 and 14.0g/kg, 1/d X 30. Results are that TZP can significantly decrease the content of blood glucose and glucose in sciatic nerve and lens of diabetic rat models. TZP is effective to reduce sorbitol content in sciatic nerve and lens(compared with negative control groups, the level of sorbitol content in the groups of higher dose of TZP decreased by 23.80% and 26.42% separately, 0.05<P<0.1), but there was no difference in inositol content in TZP treated groups. Meanwhile observed through electron-microscope ,sciatic nerve told that TZP could improve pathologic chang of SD rat’ dernyelination, axonal degeneration and mitochondria! swelling in sciatic nerve. From the above, we conclude TZP can protect diabetic rats from nervous lesion and lens lesion to a certain degree, which is relative to its hypoglycemic effect and improvement metabolism of sugar alcohols in nerve and lens tissue.4. The influence of herba TZP on renal lesions and other relative states, and anti-hyperglycemic mechanism of polysaccharide in the alloxan diabetic rat models. Results show higher doses of TZP can better rat models’ diabetic symptoms and strikingly lower the level of blood-glucose, urea nitrogen, total cholesterol, triglyceride. TZP is also effective for the inhibition of early diabetic nephromegaly, high glomerular filtration and proteinuria. Hence it is concluded that TZP has the effect of protecting the kidney of diabetic rat models to a certain degree by means of decreasing blood-glucose,cholesterol, improving renal function and hemodynamics. Besides, TZP is also effective for lowering glycosylation of hemoglobins significantly, which indicates that TZP probably has the effect for inhibition of nonenzymatic glycosylation of protein. Additionally, the hypoinsulin caused by alloxan in diabetic rat models was increased a little but with no significantvariation accompany with the hypoglycemic effect of TZP. Combined with the pathomorphology observation of pancreas, we conclude that the hypoglycemic effect of TZP has action outside pancreas, its anti-hyperglycemic mechanism is somewhat similar to drugs of biguanide ,that is, it may inhibit the absor更多还原