一氧化氮在阿托伐他汀钙抗动脉粥样硬化中的作用

Effect of nitric oxide on the antiatherogenic course of atorvastatin

摘要:

目的：观察一氧化氮（nitric oxide，NO）气体信号通路体系对他汀类降脂药物阿托伐他汀钙的抗动脉粥样硬化作用的影响。方法：雄性SD大鼠60只随机分为：正常对照组（Control组），高脂饮食组（HF组），阿托伐他汀钙（atorvastatin，ATV）组（ATV组），阿托伐他汀钙+ N’-硝基-L-精氨酸甲酯盐酸盐（N’-nitro-L-arginie methyl ester，L-NAME）组（ATV+ L-NAME组）。在给予高脂饮食后，继续ATV和ATV联合L-NAME各治疗13～15周。观察主动脉弓的病理变化；测定各组血脂水平；测量NO、总一氧化氮合酶（total-nitric oxide synthase，T-NOS）活力、内皮性一氧化氮合酶（endothelial nitric oxide synthase，eNOS）以及eNOS的信使核糖核酸（eNOSmRNA）水平。结果：与Control组相比，HF组及ATV+L-NAME组大鼠主动脉弓均出现显著的动脉粥样硬化病理损害，HF组血脂水平变化明显（P<0.05），血清NO、eNOS水平、T-NOS活力及降主动脉eNOSmRNA表达水平明显下降（P<0.05）。与HF组比较，ATV组主动脉粥样硬化病变较轻，血脂含量明显下降（P<0.05），血清NO、eNOS水平、T-NOS活力以及降主动脉eNOSmRNA表达水平明显增高（P<0.05）。与对照及ATV组别比较，ATV+L-NAME组大鼠血脂均升高明显（P<0.05），而血清 NO、eNOS含量及T-NOS活力均明显下降（P<0.05）。结论：ATV提高了大鼠血清NO体系的含量和活性，阻断大鼠NO通路后使ATV的抗动脉粥样硬化作用明显减弱。

Abstract:

Objective：To investigate antiatherosclerosis effect of atorvastatin in atherosclerosis model of SD rats，and to explore effect of nitric oxide in this course. Methods：Totally 60 male SD rats were divided into 4 groups randomly：control group，high-fat（HF） group，atorvastatin（ATV） group，and ATV+ N’-nitro-L-arginine-methyl ester hydrochloride（L-NAME） group. After being fed a high-fat diet，the rats were treated with ATV and ATV combined with L-NAME from 13 to 15 weeks，respectively. Pathologic changes of aortic arch were observed. Serum lipid level was determined. Furthermore，nitric oxide（NO），total nitric oxide synthase（T-NOS），endothelial nitric oxide synthase（eNOS） and eNOSmRNA were also determined. Results：The classical atherosclerotic lesions were fund in HF group and ATV+ L-NAME group，not in control group；serum lipid in the HF group was significantly altered（P<0.05）. Levels of serum NO，eNOS，vitality of serous T-NOS and mRNA levels of eNOS in the HF group were decreased（P<0.05）. Compared with those of HF group，atherosclerotic lesions were ameliorated in the ATV group. Serum lipid in the ATV group were significantly decreased（P<0.05）. Serum NO，eNOS，vitality of serous T-NOS and mRNA levels of eNOS in the ATV group were elevated（P<0.05）. Compared with those in ATV group，serum lipid levels in the ATV+ L-NAME group were significantly elevated（P<0.05）；serum NO，eNOS，and vitality of serous T-NOS in the ATV+L-NAME group were decreased（P<0.05）. Conclusion：Atorvastatin significantly enhances the activity of serum nitric oxide system. The blockage of nitric oxide pathway significantly bates antiatherosclerosis of atorvastatin.