烟酸对兔动脉粥样硬化斑块及MK2和骨桥蛋白表达的影响

Effect of Nicotinic Acid on Plaques Formation and Expressions of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 and Osteopontin in Aorta of Experimental Atherosclerosis Rabbit

目的探讨烟酸对兔动脉粥样硬化斑块形成(AS)和丝裂原活化蛋白激酶激活蛋白激酶2(MK2)及骨桥蛋白(OPN)的影响。方法 24只新西兰兔按随机数字表法分为对照组、高脂组和烟酸组,每组8只,对照组和高脂组分别给予普通饮食和高脂饮食14周,烟酸组给予高脂饮食8周后加用烟酸200 mg.kg-1.d-1共6周。实验前后抽血检测血脂水平,14周末进行主动脉病理学检查,采用实时荧光定量聚合酶链反应检测各组兔主动脉壁MK2 mRNA、OPN mRNA表达,采用免疫组化法检测兔主动脉壁OPN表达。结果与对照组相比,高脂组TG、TC和LDL-C显著升高(P<0.05),主动脉斑块面积明显增大(P<0.05),MK2、OPN表达显著增加(P<0.01)。与高脂组相比,烟酸组TC、TG和LDL-C显著降低(P<0.05),主动脉斑块面积显著缩小(P<0.05),MK2、OPN表达显著减少(P<0.01)。结论烟酸具有抗AS作用,其机制可能与下调OPN和MK2的表达有关。

Objective To investigate the effects of nicotinic acid on the atherosclerotic plaques formation and the expression of osteopontin（OPN） and mitogen-activated protein kinase-activated protein kinase 2（MK2） in rabbits.Methods Twenty-four New Zealand white rabbits were randomly divided into three groups： control group,hyperlipidemia group and niacin group.Control group was fed with normal diet and hyperlipidemia group with high fat diet for 14 weeks.After being fed with fat diet for 8 weeks,niacin group was fed the same fat diet plus niacin [200 mg /（kg.d） ] for 6 weeks.The blood lipid levels were detected before and after experiment.All rabbits were sacrificed to detect the histopathological changes in aortas at the end of the 14th week,real-time fluorescence quantitative polymerase chain reaction was used to detect the expressions of MK2 mRNA and OPN mRNA in aortas in each group,and immunohistochemistry was used to detect the expression of OPN in aortas.Results Compared with control group,rabbits fed with high fat diet showed higher serum levels of TC,TG and LDL-C and more aorta plaque area（P 0.05）,the expressions of MK2 and OPN increased significantly（P 0.01）.Compared with hyperlipidemia group,rabbits treated with niacin showed less serum levels of TC,TG and LDL-C and less aorta plaque area（P 0.05）,the expressions of MK2 and OPN decreased significantly（P 0.01）.Conclusion Niacin＇s role of anti-atherosclerosis may be related to its effect of down-regulating the expression of MK2 and OPN.