L-4F明显改善脂蛋白氧化张力下的血管舒张功能

L-4F dramatically improve endothelium-dependent vasodilation under lipoprotein oxidative stress

目的 探讨L 4F(一种载脂蛋白A 1类似物 )能否改善脂蛋白氧化张力下内皮依赖的血管舒张功能。方法 实验分三部分 ,均采用小鼠的颈内动脉作乙酰胆碱诱导下的内皮依赖血管舒张功能试验。第一部分采用C5 7BL6小鼠 ,分 2组 :对照组用PBS液 1L/L、L 4F组用L 4F 10mg/L预处理血管 30min。第二部分采用C5 7BL6小鼠 ,分 3组 ,对照组用RPMI 16 4 0培养液 10 0ml/L、低密度脂蛋白 (lowdensitylipoprotein ,LDL)组用LDL 10 0mg/L、LDL +L 4F组用LDL 10 0mg/L +L 4F 1mg/L预处理血管 30min。第三部分分 3组 ,对照组采用C5 7BL6小鼠 ,不作处理 ,高胆固醇血症组和L 4F组均采用低密度脂蛋白受体缺乏小鼠 ,用高脂、高胆固醇喂养 4周 ,其中高胆固醇血症组同时用生理盐水 10ml·kg-1·d-1腹膜腔内注射 (L 4F组用L 4F 1mg·kg-1·d-1)。结果 (1)L 4F本身对内皮依赖的血管舒张功能没有影响 ;(2 )L 4F可以部分改善低密度脂蛋白对内皮依赖的血管舒张功能的抑制 ;(3)L 4F可以明显改善高胆固醇血症对内皮依赖的血管舒张功能的损害 ,达到与对照组的血管舒张功能无区别。结论 L 4F可明显改善脂蛋白氧化张力下内皮依赖的血管舒张功能 。

Objective To investigate the effect of L-4F, an apolipoprotein A-1 mimetic, in improving endothelium-dependent vasodilation under lipoprotein oxidative stress. Method The experiment was divided into 3 parts, using the acetylchol ine-induced vasodilation of isolated carotid arterioles from mice. In part 1, C 57BL6 mice were used and divided into two groups. The vessels were pretreated wi th PBS 1 L/L in control group and with L-4F 10 mg/L in L-4F group for 30 min. In Part 2, C57BL6 mice were used and divided into three groups. The vessels were pretreated with 100 ml/L of RPMI 1640 in control group, with low density lipopr otein (LDL) 100 mg/L in LDL group and with LDL 100 mg/L+L-4F 1 mg/L in L-4F+ LDL group for 30 min. In part 3, mice were divided into three groups. C57BL6 mic e were used in control group without treatment. In group 2, LDL receptor defic iency (LDLr_-/- ) mice were used and fed on a high fat and cholesterol diet for 4 weeks with saline 10 ml·kg_-1·d_-1 ip. In group 3, LDLr_-/ - mice were used and fed on a high fat and cholesterol diet for 4 weeks with L-4F 1 mg·kg_-1·d_-1 ip. Results (1) L-4F itse lf had no effect on endothelium-dependent vasodilation; (2) L-4F can partially protect vasodilation by blocking the inhibiting effects of LDL; (3) L-4F can i mprove vasodilation from hypercholesterolemia of the LDLr_-/- mice to the e xtent that its vasodilation was indistinguishable from that of controls. Conclusion _L-4F can dramatically improve endothelium-dependent v asodilation under lipoprotein oxidative stress and the results may provide a new therapeutic approach in treating vascular diseases such as atherosclerosis in t he future.