卡托普利对糖基化终产物损伤大鼠血管内皮功能的保护作用

Protective effects of captopril on impaired vascular endothelial function induced by AGEs

目的研究卡托普利对外源性制备的糖基化终末产物损伤大鼠离体胸主动脉环内皮依赖性舒张功能的影响及其机制。方法按文献方法制备糖基化终末产物,采用外源性糖基化终末产物(AGE-BSA)孵育大鼠离体胸主动脉环90 min诱导血管内皮功能的损伤,并观察卡托普利、超氧化物歧化酶和L-精氨酸对糖基化终末产物所致的血管内皮依赖性舒张反应损伤的影响。结果外源性糖基化终末产物孵育大鼠离体胸主动脉环90 min,明显抑制乙酰胆碱诱导的内皮依赖性血管舒张反应(endothelium-dependent relaxation,EDR)。但对硝普钠诱导的内皮非依赖性血管舒张反应没有影响。卡托普利(3、10和30μmol.L-1)与AGE-BSA共同孵育血管环90 min,浓度依赖性地改善AGE-BSA对血管内皮依赖性舒张反应的损害。依那普利拉、氧自由基清除剂超氧化物歧化酶(superoxidedismutase,SOD,200 U.mL-1)也可改善AGE-BSA对内皮依赖性血管舒张反应的损害,而L-精氨酸(L-argi-nine,L-Arg,3 mmol.L-1)却没有明显的保护作用。结论卡托普利对AGE-BSA所引起的血管内皮依赖性舒张反应的损害具有明显的保护作用,该作用可能与其抗氧化作用有关,同时可能是部分巯基依赖性的。

Objective To explore whether captopril has protective effect on impaired vascular endothelial function elicited by exogenous AGEs and to investigate the potential mechanisms. Methods AGEs were prepared according to the methods from literatures. The rings were respectively incubated with exogenous AGEs to induce endothelial dysfunction, and with captopril, SOD, and L-arginine to investigate the effects of these drugs on impaired vascular endothelial function elicited by exogenous AGEs. Results In vitro experiments showed that a 90 min incubation of aortic rings with AGEs resulted in a significant inhibition of endothelium-dependent relaxation （EDR）, but had no effects on endothelium-independent relaxation. Captopril （3, 10, and 30μmol · L^-1）, enaprilat （30μmol · L^-1） and SOD （200 U · mL^-1） can attenuate the inhibition of EDR caused by AGEs, but L-Arg had no significant protective effects. Conclusion Captopril can protect against vascular endothelial dysfunction caused by AGE-BSA. The protective effects of captopril may be related to its anti-oxidation and may be partly sulfhydryl-dependent.