新型糖原磷酸化酶抑制剂山楂酸对Ⅱ型糖尿病大鼠的神经保护作用(英文)  

Neuroprotection of Maslinic Acid,a Novel Glycogen Phosphorylase Inhibitor,in Type 2 Diabetic Rats

作　　者：关腾[1] 钱贻崧[1] 黄梦昊[1] 黄龙飞[1] 汤旭蓁[1] 李运曼[1] 孙宏斌[2] 

机构地区：[1]中国药科大学生理教研室 [2]中国药科大学新药研究中心,南京210009

出　　处：《中国天然药物》2010年第4期293-297,共5页

基　　金：supported by National Natural Science Foundation of China (Nos. 30672523 and 90713037);research grants from Chinese Ministry of Education (Nos. 706030 and 20050316008)~~

摘　　要：目的:探讨新型糖原磷酸化酶抑制剂山楂酸(MA)对高血糖大鼠脑缺血/再灌损伤的作用。方法:通过高脂饮食(HFD)合并低剂量链脲佐菌素(STZ)注射,制作II型糖尿病大鼠模型。不同剂量MA(10,5和2.5mg·kg?1·d?1)灌胃2周。双侧颈总结扎诱导建立大鼠脑缺血模型,评价MA对脑缺血/再灌II型糖尿病大鼠神经保护作用。结果:MA可显著降低II型糖尿病大鼠的空腹血糖(GLU)、血浆甘油三酯(TG)和总胆固醇(TC)水平。脑缺血II型糖尿病大鼠脑组织中丙二醛(MDA)含量显著增高,超氧化物歧化酶(SOD)活性显著下降;缺血3d后海马CA1区可观察到显著神经元损伤。MA显著减轻脑缺血损伤,并呈剂量依赖性。此外,MA可显著降低皮层和海马区MDA含量,减轻脑组织的脂质过氧化反应,提高缺血再灌大鼠脑组织的SOD活性。结论:MA预作用对II型糖尿病合并脑缺血诱导的损伤具有良好的保护作用。AIM：To investigate the effects of maslinic acid（MA）,a novel glycogen phosphorylase inhibitor in hyperglycemic rats after cerebral ischemia/reperfusion injury.METHODS：Rats were fed with high fat diet（HFD） followed by low-dose streptozotocin（STZ） injection to induce metabolic syndrome.Three doses of MA（10,5 and 2.5 mg·kg？1·d？1） were administered once daily by i.g.for 2 weeks.Neurological outcomes were compared in vehicle and MA treated HFD/STZ rats with cerebral ischemia/reperfusion injury induced by bilateral common carotid artery occlusion.RESULTS：The elevation of plasma fasting glucose（GLU）,serum plasma triglyceride（TG） and plasma total cholesterol（TC） was antagonized by MA significantly.Cerebral ischemia with pre-existing hyperglycemia and hyperlipemia caused prominent elevation in MDA levels and decrease in SOD activity.Extensive neuronal death occurred in the CA1 area of hippocampus at day 3 after forebrain ischemia.MA significantly attenuated ischemia-induced neuronal death in a dose-dependent manner.Moreover,MA caused a significant reduction in MDA levels and elevation in SOD activity in both cortex and hippocampus.CONCLUSION：Results suggested the prophylaxis of MA may also show beneficial effects in reducing cerebral damage after stroke for patients with type 2 diabetes.

关 键 词：糖原磷酸化酶 山楂酸 神经保护 II型糖尿病 

分 类 号：R969.4[医药卫生—药理学]