| Objective: To observe the anti-atherosclerosis (AS) effects of Levamlodipine Besylate andcombined with rosuvastatin after abdominal balloon endothelial injury in New Zealand rabbits,and to explore the mechanism from the perspective of anti-inflammatory and plaque stability.Materials and Methods:54rabbits were randomly divided into five groups: sham group, modelgroup, Levamlodipine group, rosuvastatin group and the combination drug group. Model groupreceived high-fat diet and abdominal aortic balloon endothelial injury surgery, Levamlodipinegroup received Levamlodipine2.5mg/d on the basis of the model group, and rosuvastatin groupreceived rosuvastatin1.5mg/kg/d, and the combination group received Levamlodipine2.5mg/dand rosuvastatin1.5mg/kg/d, we measured and compared the level of serum lipids,high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-a (TNF-a), lipoproteinphospholipase A2(Lp-PLA2) and type1plasminogen activator inhibitor (PAI-1) before surgeryand8weeks after surgery with ELISA, we also performed abdominal aortic angiography andvascular ultrasound before killed. All animals were killed at8weeks after surgery, and thoracicaorta (not injured by balloon) and abdominal aorta (injured by balloon) were cut down asspecimens, HE staining for pathological morphological analysis, and immunohistochemicalstaining for examining the express of matrix metalloproteinase-3(MMP-3) and macrophagemigration inhibitory factor (MIF) within the plaque.Results:1, Survival rate of animals after surgery was about80%.2, Levamlodipine tended to decrease serum LDL-C level comparing with the model group (16.24vs19.41mmol/L, P=0.08, no significant difference). All groups(except sham group)had nodifference on the level of serum TC, TG and HDL-C.3, The level of serum Hs-CRP, Lp-PLA2, and PAI-1of Levamlodipine group had no significantdifference with the model group (P>0.05), while the level of serum TNF-a was significantly higher than model group (P <0.05).4, The average abdominal aortic plaque thickness of Levamlodipine group was lower than themodel group (313.56vs405.93um), but no statistical significance (P=0.12), but the thoracicaortic plaque thickness and intimal hyperplasia index of Levamlodipine group were significantlylower than the model group (112.36vs180.57um,0.18vs0.32, P <0.05). Abdominal aorticplaque thickness and intimal hyperplasia index of combination group were lower than theLevamlodipine group (P <0.05).5, The expression of MMP-3and MIF within the plaque of levamlodipine group wassignificantly less than model group (52.45%vs70.84%,43.09%vs77.04%, P <0.05).Conclusion:1, High-fat diet combined with abdominal aortic balloon endothelial injury can successfullybuild up AS animal model in rabbit, the survival rate is high.2, Levamlodipine tends to lower serum LDL-C.3, Levamlodipine can not significantly inhibit intimal hyperplasia after vessel endothelial injury,but can significantly postpone the progress of atherosclerosis after high-fat diet.4, Levamlodipine plaque can increase the stability of the plaque by reducing the expression ofMMP-3and MIF.5, Levamlodipine combined with rosuvastatin can enhance the anti-atherosclerosis effect ofLevamlodipine. |
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