目的 观察灵芝多糖和二甲双胍联用对糖尿病大鼠胸主动脉晚期糖基化终末产物（AGEs）和结缔组织生长因子（CTGF）表达的影响。方法 SD大鼠采用高能量饮食4周加ip小剂量链脲佐菌素（STZ）30 mg/kg建立2型糖尿病模型。成模后随机分为模型组、灵芝多糖（600 mg/kg）组、二甲双胍（600 mg/kg）组及联合用药组（灵芝多糖300 mg/kg＋二甲双胍300 mg/kg），另设对照组。给药治疗12周末测定大鼠空腹血糖、血浆胰岛素、血清AGEs；测定血清过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）活性；电镜超微结构观察胸主动脉病理改变；免疫组化和蛋白印记法检测胸主动脉AGEs及CTGF蛋白的表达。结果 联合用药组能显著降低糖尿病大鼠空腹血糖，升高血浆胰岛素水平，降低血清AGEs的量及升高血清CAT、GSH-Px活性，减少胸主动脉AGEs及CTGF的表达，减轻胸主动脉病变过程。结论 灵芝多糖联合二甲双胍可能通过抑制主动脉氧化应激、降低血清AGEs水平以及下调主动脉AGEs、CTGF的表达，从而对糖尿病大鼠主动脉起到保护作用。

Objective To study the effects of Ganoderma lucidum polysaccharides (GLPs) and metformin (Met) on the expression of advanced glycosylation end products (AGEs) and connective tissue growth factor (CTGF) in thoracic aorta of diabetic rats. Methods SD rats were fed with high fat diet for 4 weeks, and injected with streptozotocin (STZ, 30 mg/kg) to establish type 2 diabetic model. The diabetic rats were randomly divided into diabetes group, GLPs group (600 mg/kg), Met group (600 mg/kg), combination group (GLPs 300 mg/kg + Met 300 mg/kg), and normal control group. After 12 weeks' treatment, the levels of fasting serum glucose, insulin in plasma, AGEs in serum, the activity of catalase (CAT) and glutathione peroxidase (GSH-Px) were detected. The pathological changes of thoracic aorta were examined by electron microscope. Immunohistochemical and Western blotting methods were used to detect AGEs and CTGF protein expression in thoracic aorta. Results Combination group could lower the fasting blood glucose significantly, raise the insulin level in plasma, improve the activity of CAT and GSH-Px in myocardium, decrease the concentration of AGEs in serum, reduce the expression of AGEs and CTGF in thoracic aorta, and relieve the pathological change process of thoracic aorta. Conclusion GLPs combined with Met shows the protective effect on the thoracic aorta in diabetic rats. The possible mechanism may be related to inhibit the oxidative stress of thoracic aorta, lower AGEs level in serum, and do some down regulation of AGEs and CTGF in thoracic aorta.

科技部“十一五”国家科技支撑计划子课题项目（2006DAI06A20-02）；江苏省优势学科项目