The Effects Of Different Enantiotopic Amlodipine On Serum MMP-3,MMP-9and CRP In Rabbits Atherosclerosis Model

Objective：Amlodipine is now one of the most widely used calciumantagonists. Racemic amlodipine is composed of S-amlodipine andR-amlodipine in the form of1:1. Study has demonstrated that amlodipine maybe effective in preventing the development of atherosclerosis, but until nowwe do not know which part has the effect of anti-atherosclerosis. Matrimetalloproteinases are believed to contribute to the development and theprogression of atherosclerosis by breaking down extracellular matrix.Evidence suggests that CRP is not only an impotant and unique risk maker, butalso has a role in the pathogenesis of inflamation and atherosclerosis. Toinvestigate the effects of different enantiotopic amlodipine on atherosclerosis,we measured MMP-3, MMP-9and CRP in high fat diet fed rabbits, which fedwith S-amlodipine, R-amlodipine or Racemic amlodipine, respectively.Methods:30male New Zealand rabbits were randomized allocated in4groups：control group (group A, n=9), S-amlodipine group (group B, n=7),R-amlodipine group (group C, n=7), and racemic amlodipine group (group D,n=7). All the rabbits in the4groups were fed on a high-cholesterol diet(1%cholesterol and2%lard oil) for8weeks, and meanwhile rabbits in group B, Cand D were administrated with S-amlodipine (2.5mg/d), R-amlodipine(2.5mg/d) and racemic amlodipine (5mg/d) for8weeks, respectively. Bloodsamples were collected at the baseline of the study, the4thweek and the8thweek. The concentration of TC, LDL-C, HDL-C and TG were measured. Atthe same time, the serum concentration of MMP-3and MMP-9were measuredby enzyme linked immunoadsorbent assay (ELISA), and the serumconcentration of CRP was measured by immunization project turbidity. Dataare analyzed by SPSS13.0software packet, and all measurement data wereshown as±SD. Comparisions among groups were performed by ANOVA. When the variance analysis can not meet the conditions, Kruskal-Wallis testwas used. Between groups were compared with SNK-q. A p value<0.05wasconsidered statistically significant.Results：1The effects of different enantiotopic amlodipine on TC, LDL-C,HDL-C and TG level in the rabbits serum in different period.1.1At the baseline, compared with the control group, the levels of serumTC, LDL-C, HDL-C and TG were not different significantly (P>0.05).1.2At the4thweek, the levels of serum TC, LDL-C, HDL-C and TG inall4groups were increased, and there were no significant difference amonggroups (P>0.05).1.3At the8thweek, the levels of serum TC, LDL-C, HDL-C and TG wereincreased, but there were no significant difference among groups (P>0.05).2The effects of different enantiotopic amlodipine on serum MMP-3levelin the rabbits2.1The levels of serum MMP-3were not significantly different amongthe S-amlodipine group, the R-amlodipine group, the racemic amlodipinegroup and the control group at the basetime(F=0.127, P=0.943>0.05). Theserum concentration of MMP-3in each group was evidently higher at the4thweek than at the basetime, but there were no difference among the controlgroup and the drug-therapy groups(F=0.572, P=0.639>0.05). There were nosignificant difference among the groups at the8thweek, too(F=2.249,P=0.108>0.05).3The effects of different enantiotopic amlodipine on MMP-9level in therabbits serum3.1The levels of serum MMP-9were no significant difference among theS-amlodipine group, the R-amlodipine group, the racemic amlodipine groupand the control group at the baseline(F=0.359, P=0.783>0.05). The serumconcentration of MMP-9in every group was evidently higher at the4thweekthan the basetime, but the level of serum MMP-9in the racemic amlodipinegroup was significantly lower than that in the other groups, and the serum levels of MMP-9in the drug-therapy groups were lower than that in thecontrol group(F=3.748, P=0.024<0.05). The level of serum MMP-9in theracemic amlodipine group was clearly lower than that in other groups, and theserum levels of MMP-9in the drug-therapy groups were lower thanthat in thecontrol group at the8thweek(F=5.166, P=0.007<0.01).4The effects of different enantiotopic amlodipine on CRP level in therabbits serum4.1The levels of serum CRP were not significantly different among theS-amlodipine group, the R-amlodipine group, the racemic amlodipine groupand the control group at thebaseline(F=1.853, P=0.162＞0.05). The serumconcentration of CRP in every group was evidently higher at the4thweek thanthat at the basetime, but the level of serum CRP in the drug-therapy groupswere lower than that in the control group(F=11.653, P=0.000<0.01). At the8thweek, compared with the control group, the serum concentration of CRP inother groups were lowered, and the levels of serum CRP in the S-amlodipinegroup and the R-amlodipine group were evidently higher than that in theracemic amlodipine group(F=51.269, P=0.000<0.01).Conclusion：1The leves of serum TC, LDL-C, HDL-C and TG in the rabbits ofhigh-cholesterol diet were significantly increased. The serum concentration ofMMP-3, MMP-9and CRP were increased, too.2Different enantiotopic amlodipine did not change the concentration ofTC, LDL-C, HDL-C and TG in the atherosclerotic rabbits serum.3Different enantiotopic amlodipine did not change the serumconcentration of MMP-3in the atherosclerotic rabbits. Different enantiotopicamlodipine could decrease the levels of serum MMP-9and CRP. The racemicamlodipine was better than S-amlodipine and R-amlodipine, and theS-amlodipine was better than R-amlodipine. There were statistical difference.