Cariporide对高脂血症引起的兔血管内皮功能损伤的保护作用

Protective effect of Na^+-H^+ exchanger inhibitor cariporide on the injury of vascular endothelial function induced by hypercholesterolemia

目的 :探讨选择性钠氢交换抑制剂cariporide对高胆固醇和高脂肪 (HCHF)饮食所致的兔动脉粥样硬化血管功能损伤的保护作用。方法 :将 2 2只雄性新西兰白兔随机分为 3组 :正常对照组 (n =6 )、HCHF饮食组 (n =8)、cariporide治疗组 (HCHF饮食 +cariporide ,n =8)。在HCHF饲养前和饲养后第 10周分别称重 ,抽血测血清总胆固醇浓度。第 10周后处死动物 ,取胸主动脉检测血管功能。结果 :①高脂血症兔胸主动脉对乙酰胆碱 (ACh)引起的内皮依赖性舒张 (EDR)反应明显降低 ,cariporide能明显保护HCHF血症所损伤的EDR反应。②cariporide对硝普钠所致的非内皮依赖性舒张反应无影响。③cariporide对HCHF饮食时血清总胆固醇浓度的改变无影响。结论 :cariporide对HCHF血症所致血管内皮功能损伤具有保护作用。提示HCHF饮食所致动脉粥样硬化血管功能损伤可能牵涉细胞膜钠氢交换体的活化。

Objective To explore possible effects of cariporide, a new Na + H + exchanger (NHE 1) inhibitor, against injuries of vascular endothelial function induced by hypercholestrolemia. Methods Twenty two healthy New Zealand rabbits were randomly divided into 3 groups: Six were fed with normal diet as the control; eight were fed with high cholesterol plus high fat diet (HCHF)as the injured control group; and the other eight were fed with HCHF plus cariporide orally (0.1 mg/kg·d 1 ) as the treated group. The animals were weighed and their blood was drawn from the central ear artery to analyze plasma cholesterol at the pre experiment and in the 10th week of postexperiment. The animals were killed in the 10th week and the aortic artery was isolated to analyze vascular endothelial function. Results ①The HCHF diet significantly attenuated endothelium dependent relaxation (EDR) of rabbit aortic rings to acetylcholine (ACh), but cariporide significantly protected against HCHF diet injured EDR of rabbit aortic rings. The dose response curves elicited by ACh from HCHF diet rabbits were more significantly shifted to the right than those from HCHF diet plus HOE 642 treated rabbits. ②The HCHF diet and cariporide did not significantly influence the endothelium independent relaxation of the rabbit artery elicited by sodium nitroprusside (SNP). ③ There was no significant difference in the levels of total cholesterol and LDL C between the HCHF diet and the HCHF diet plus cariporide rabbits. Conclusion The Na + H + exchanger (NHE 1) inhibitor can protect against injuries of vascular endothelial function induced by hypercholesterolemia . The activized Na + H + exchangers of cellular membranes may be involved in injuries of vascular endothelial function induced by hypercholesterolemia.