| Background Atherosclerosis is one of the main diseases that harms to health of human beings. It is also the major causes of morbidity and mortality in patients with cardiovascular disease. However, despite widespread use of statin therapy, residual cardiovascular risk remains. Therefore, it becomes one of tactics of anti-AS treatment for us to keep looking for the auxiliary medicine which can optimize lipid profiles and reduce risk further. Nicotinic acid has got a lot of attentions because of its comprehensive and unique effect on lowering lipid and increasing HDL-C. Recent studies found that the "old drug" has an obvious anti-atherogenic effect and also can significantly reduce the incidence and mortality of coronary heart disease. The mechanism of anti-atherogenic effect of nicotinic acid so far hasn't been completely confirmed yet. Apart from being related with pleiotropic role of nicotinic acid in lipid-lowering, It may also be relevant with that Nicotinic acid can suppress the expressions of signal transducer and cytokine participating several pathologic processes in AS, such as inflammation, oxidative stress, cell proliferation and cell transfer.Mitogen-Activated Protein Kinases -activated protein kinase 2(MK2) is an important signal transducer in the channels of mitogen-activated protein kinases (MAPK), while Osteopontin (OPN) is an important cytokine of extracellular matrix. they both were implicated in development of AS with modulating the pruduction of inflammatory factor , recruiting macrophage,promoting proliferation and movements of smooth muscle cells, and promoting development of atherosclerotic plaque et al. The effect that Nicotinic Acid has on the expressions of MK2 and OPN so far hasn't been reported.Objective To investigate the effects of nicotinic acid on the expressions of MK2 and OPN in aorta of experimental atherosclerotic rabbits, and to provide evidence for the further application of nicotinic acid in anti- arteriosclerosis.Methods 16 rabbits that were randomly selected from 24 New Zealand white rabbits were fed with high-fat diet for 8 weeks, and then were randomly divided into two groups:①hyperlipidemia group(n=8): maintained high-fat diet for another 6 weeks;②nicotinic acid group(n=8):the same fat diet supplemented with nicotinic acid(200mg·kg-1·d-1)for another 6 weeks. The rest 8 rabbits were fed with normal diet for 14 weeks as control group (n=8). We measured the blood lipid level and body weight before and at the the end of 8th and 14th week of experiment.At the end of the experiment, the rabbits were killed for making aorta specimen. Then the histopathological changes of the aortas were analyzed, the expressions of MK2 and OPN mRNA in the aortas were detected by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), and the expression of OPN protein in aortas was detected by immunohistochemistry.Results Compared to control group, the levels of total cholesterol, triglyceride and LDL cholesterol of hyperlipaemia group were significantly increased, and so were area of atherosclerotic plaque, intimal thickness of aorta and expressions of MK2 mRNA, OPN protein and OPN mRNA (P <0.01); Compared to hyperlipaemia group, levels of total cholesterol, triglyceride and LDL cholesterol of niconitic acid group were reduced significantly (P <0.01) , while HDL-Cholesterol was obviously increased (P <0.01). Area of atherosclerotic plaque and intimal thickness of aorta were reduced significantly, and so were expressions of MK2 mRNA, OPN mRNA and protein (P <0.01). Based on correlation analysis , expressions of MK2 mRNA(r=0.919,P<0.01),OPN mRNA(r=0.888,P<0.01)and OPN protein (r=0.821,P<0.01)were all positively correlated with area of atherosclerotic plaque, while expressions of MK2 mRNA(r=0.863,P<0.01),OPN mRNA(r=0.874,P<0.01)and OPN protein(r=0.818,P<0.01) were all positively correlated with intimal thickness of aorta.Conclusion Nicotinic acid has anti-atherogenic effect. The anti-atherogenic effect of nicotinic acid is not only related with pleiotropic role of nicotinic acid in lipid-lowering, but also may be related with that Nicotinic acid can down regulate the expressions of MK2 and OPN. |
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