洛伐他汀对低密度脂蛋白损伤血管内皮的保护作用

目的：探讨洛伐他汀对低密度脂蛋白所致血管内皮功能损伤的保护作用及可能的机制．方法：一次性从大鼠舌下静脉注射天然低密度脂蛋白(n-LDL 4mg／kg),在舌下静脉注射n-LDL之前大鼠腹腔注射洛伐他汀(2或4mg／kg),每天一次,连续五天．注射n-LDL后48小时检测乙酰胆碱诱导的血管内皮依赖性舒张(EDR)及血清一氧化氮(N0)、丙二醛(MDA)的含量和超氧化物歧化酶(SOD)的活性．结果：一次注射n-LDL导致了EDR、血清NO水平及SOD活性明显降低,MDA的浓度明显增高。预先给予洛伐他汀能明显减轻LDL引起的EDR的抑制和血清NO水平及SOD活性的降低,减少MDA的生成,左旋硝基精氨酸(L-NNA)减弱洛伐他汀对血管内皮的保护作用．结论：洛伐他汀对LDL损伤的血管内皮具有保护作用,可能与保护内皮依赖性松弛因子和抗氧化作用有关。

Protective effects of lovastatin on vascular endothelium injured by low density lipoprotein

AIM: To examine protective effects of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on endothelial dysfunction induced by a single intravenous injection of natural low density lipoprotein (n-LDL) and analyze the possible action mechanism of lovastatin. METHODS: Rats were treated by intraperitoneal injection with lovastatin at dose of 2 or 4 mg/kg body weight once daily for 7 d, and on d 6 a single injection of n-LDL 4 mg/kg was given by sublingual vein. Forty eight hours after injection of n-LDL, the descending thoracic aorta of rats was taken. Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelium-independent relaxation of aortic rings were examined in vitro. Malondialdehyde (MDA), nitric oxide (NO), and activity of superoxide dismutase (SOD) as well as level of lipid in serum were analyzed. RESULTS: A single injection of n-LDL inhibited ACh-induced EDR compared with normal control group (maximal relaxation rate: 69.5 %+/-1.2 % vs 91.0 %+/-1.2 %, P<0.05), decreased serum NO level [(7.0+/-0.5) micromol/L vs (11.2+/-0.9) micromol/L, P<0.05] and serum SOD activity [(371+/-16) kNU/L vs (405+/-18) kNU/L, P<0.05] and elevated serum MDA level [(5.4+/-0.5) micromol/L vs (3.0+/-0.8) micromol/L, P<0.05]. Compared with n-LDL treated group, lovastatin 2 and 4 mg/kg increased EDR( maximal relaxation rate 82.9 %+/-0.5% and 83.7 %+/-0.7 % vs 69.5 %+/-1.2 %, P<0.05) and elevated NO level [(11.0+/-0.7) and (11.2+/-0.8) micromol/L vs (7.0+/-0.5) micromol/L, P<0.05], increased SOD activity [(402+/-15) and (408+/-25) kNU/L vs (371+/-16) kNU/L, P<0.05], and reduced serum MDA level [(3.3+/-0.6) and (3.5+/-0.4) micromol/L vs (5.4+/-0.5) micromol/L, P<0.05]. But sodium nitroprusside-induced endothelium-independent relaxation and the level of serum lipid in both saline+LDL group and lovastatin-treated group had no marked alteration. CONCLUSION: Lovastatin was able to protect vascular endothelium from dysfunction induced by a single injection of n-LDL.