晚期糖基化终产物裂解剂C24对糖尿病大鼠心血管作用

目的研究新型化合物C24裂解晚期糖基化终产物(AGEs)蛋白交联结构及其对糖尿病大鼠心血管功能的作用,从而为开发新型AGEs裂解剂提供实验依据。方法酶联免疫吸附测定(ELISA)法测定C24体外裂解AGEs交联结构作用。通过血流动力学实验观察C24对长期糖尿病大鼠心血管的作用,观察C24对大鼠尾胶原溶解性的影响。结果C24能够裂解体外形成的AGEBSA胶原交联结构,能够显著增加糖尿病大鼠心输出量(P<0.05)、降低总外周阻力(P<0.01)、提高动脉顺应性(P<0.05)。生化检测表明,C24能够显著增加糖尿病大鼠尾胶原溶解性(P<0.05),裂解体内AGEs交联结构。结论C24能够裂解体内及体外AGEs交联结构,改善糖尿病大鼠心血管功能。

Cardiovascular effects of advanced glycation endproducts breaker(C24)in diabetic rats

Objective To examine the effects of a novel AGEs breaker,C24,on the development of cardiovascular disease in experimental diabetic rats.Methods A special ELISA technique was used to evaluate the ability of C24 to break the crosslinks of glycated-BSA(AGE-BSA)to a rat tail tendon collagen in vitro.Diabetic Wistar rats were made by injecting streptozotocin and kept for 12 weeks.After another 4 weeks treatment with vehicle or C24(10 mg/kg·d),cardiovascular systemic hemodynamics measurements in anesthetized rats were processed through a fluid-filled catheter and an adapted Doppler probe respectively by digital converter of BIOAC System.The collagen solubility against limited pepsin digestion in tail tendon collagen were also detected.Results In vitro study showed that C24 could concentrationdependently break the crosslinks of glycated-BSA(AGE-BSA)on rat tail tendon collagen.In hemodynamic study of cardiovascular system,significantl increase in cardiac output(P<0.05)was observed after the treatment of C24(10 mg·kg~(-1))for 4 weeks.Meanwhile,a reduction of total peripheral resistance(P<0.01) and an increase of systemic arterial compliance(P<0.05) compare with that of to vehicle-treated diabetic rats.Biochemical study showed that C24 could significantly increase collagen solubility(P<0.05).Conclusions C24,a novel AGE breaker,has the ability to break AGE crosslinks in vivo and in vitro,and it can restore diabetes-associated cardiovascular disorders in rats.The study provides a potential therapeutic approach for cardiovascular disease in human diabetes.