目的 观察盐酸二甲双胍(metformin hydrochloride,MH)对2型糖尿病大鼠波动性高血糖状态下血管内皮功能的影响.方法 采用高脂饲料喂养加链脲佐菌素(streptozotocin,STZ) 35 mg·kg-1腹腔注射建立2型糖尿病(T2DM)大鼠模型,并依照空腹血糖变异系数将造模成功的T2DM大鼠分为波动高糖组和稳定高糖组,并将波动高糖组随机分为3组:MH 150 mg·kg-1·d-1组、300 mg·kg-1·d-1组和波动高糖对照组.药物干预8周,观察盐酸二甲双胍对波动性高血糖大鼠主动脉内皮,血浆肝细胞生长因子(HGF)、血浆糖基化终末产物(AGEs)、氧化型低密度脂蛋白受体-1盐酸二甲双胍组大鼠血浆HGF、AGEs、LOX-1及血清TNF-α、sICAM-1均较波动高糖组降低,血清抗氧化能力改善.结论 二甲双胍具有减轻血糖波动T2DM大鼠血管内皮损伤的作用,其保护作用可能与其减少脂质过氧化产物的产生,增强机体的抗氧化能力,减轻炎症反应,减少细胞黏附因子表达及糖基化终末产物的蓄积有关.%Aim To observe the effects of metformin hydrochloride( MH ) on the endothelial function of type 2 diabetes mellitus rats with high blood glucose fluctuation. Methods The T2DM rats models were created by intraperitoneal injection of a small dose of streptozotocin( STZ, 35mg · kg-1 ) plus high fat diet. Then diabetic rats were divided into steady high glucose ( SHG ) group and fluctuant high blood glucose ( FHG ) group, according to fasting blood coefficient of variation ( FBG-CV ), then the FHG group was randomly divided into three groups: MH 150 mg · kg-1 · d-1 group,MH 300 mg · kg-1 · d-1 group and fluctuant high blood glucose control group. Meanwhile, animals without any treatment were used as normal control. Eight weeks later, the aortic arteries tectology,plasma Hepatocyte growth factor ( HGF ), advanced glycation end products( AGEs ), lectin-like oxidized cellulose low density lipoprotein receptor-l( LOX-1 ), and serum antioxidant ability, tumor necrosis factor-α, and soluble intercellular adhesion molecule 1 were measured. Result In comparison with fluctuant high blood glucose control group, the plasma HGF, AGEs, LOX-1 and serum TNF-α, slCAM-1 in MH groups were all significantly decreased, meanwhile the serum antioxidant ability of MH groups was improved. Conclusion Metformin hydrochloride can improve the endothelial function of type 2 diabetes mellitus rats with high blood glucose fluctuation, which may be related to its effects of reinforcing antioxidant ability, decreasing AGEs and LOX-1 production and reducing inflammatory reaction.
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