依哲麦布联合辛伐他汀对动脉粥样硬化大鼠血脂、C反应蛋白的影响及意义

The effects and significance of ezetimibe combination with simvastain on C- reaction protein and lipid in rats with atherosclerosis

目的证实依折麦布(ezetimibe)联合辛伐他汀(simvastain)强化降脂治疗的作用,探索其在抑制动脉粥样硬化形成方面的作用。方法选取雄性SD大鼠60只,随机分为正常组、动脉硬化组、辛伐他汀组、依折麦布辛伐他汀组。正常组普通饲料喂养,其余3组高脂饲料喂养14周建立动脉粥样硬化模型后,辛伐他汀组给予辛伐他汀,依折麦布辛伐他汀组给予依折麦布及辛伐他汀灌胃干预4周,18周末处死大鼠。4组均采血检测血脂、C反应蛋白(CRP)含量,分离腹主动脉和肝脏,经苏木精-伊红(HE)染色观察主动脉和肝脏病理,主动脉制备匀浆,免疫比浊法检测粥样斑块内CRP的含量。结果动脉硬化组胆固醇(CHOL)、甘油三酯(TG)、低密度脂蛋白(LDL)水平显著升高(P<0.05),高密度脂蛋白(HDL)水平减低(P<0.05);辛伐他汀组、依折麦布辛伐他汀组较动脉硬化组TG、CHOL、LDL水平明显降低(P<0.05),HDL水平升高(P<0.05);依折麦布辛伐他汀组较辛伐他汀组TG、CHOL、LDL水平降低(P<0.05),HDL水平升高(P<0.05)。动脉硬化组血清及主动脉内CRP含量较正常组明显升高(P<0.05),辛伐他汀组、依折麦布辛伐他汀组CRP含量较动脉硬化组明显降低(P<0.05),依折麦布辛伐他汀组较辛伐他汀组CRP含量降低(P<0.05)。动脉硬化组肝脏可见脂质空泡,呈弥漫性并有融合现象,辛伐他汀组肝细胞脂肪变性程度减轻,依折麦布辛伐他汀组较辛伐他汀组减轻程度增加。动脉硬化组内膜增生较明显,与其相比较辛伐他汀组、依折麦布辛伐他汀组内膜厚度变薄,辛伐他汀组、依折麦布辛伐他汀组2组之间比较差异无统计学意义(P>0.05)。结论依折麦布联合辛伐他汀具有强化降脂及抑制肝细胞脂肪变性的作用,能够明显降低CRP含量,但未能抑制动脉粥样硬化的形成。

Objective To study the effects of ezetimibe combination with simvastain on C- reaction protein and lipid in rats with atherosclerosis and to explore the interventional mechanism. Methods SD rats were randomly divided into normal group,atherosclerosis group,ezetimibe group and ezetimibe combination with simvastain group. The atherosclerosis model was established by High- fat diet. The ezetimibe group and ezetimibe combination with simvastain group rats were respectively administrated with ezetimibe and simvastain at 2mg / kg / d intragastrically as intervention,while distilled water was given to other groups. After 18 weeks,the serum levels of blood lipid and C- reaction protein were observed. The levels of C- reaction protein in atheromatous plaque were analyzed by immune turbidimetry. The pathological changes of aorta and liver were observed by HE staining. Results The levels of Cholesterol（ CHOL）,triglyceride（ TG） and low density lipoprotein cholesterol（ LDL） were significantly higher in the atherosclerosis rats than in control group（ P〈0. 05）. The level of high- density lipoprotein cholesterol（ HDL） were lower in the atherosclerosis rats than in control group（ P〈0. 05）. Compared with the atherosclerosis group,the levels of Cholesterol（ CHOL）,triglyceride（ TG） and low density lipoprotein cholesterol（ LDL） were significantly lower in simvastain and ezetimibe combination with simvastain group（ P〈0. 05） and the level of high-density lipoprotein cholesterol（ HDL） were higher（ P〈0. 05）. Meanwhile,the level of C- reaction protein in the aorta and serum in the atherosclerosis group were higher than the normal group（ P〈0. 05）. Compared with the atherosclerosis group,the level of C- reaction protein in the aorta and serum in simvastain group and ezetimibe combination with simvastain group were lower（ P〈0. 05）. There were lipid vacuoles in the liver and arterial intima hyperplasia in the aorta. However,hepatocyte fatty degeneration and arterial intima hyperplasia were improved in the ezetimibe combination with simvastain group. Conclusion The ezetimibe combined with simvastain can improve the level of lipid and inhibit the action of hepatocyte fatty degeneration,which can significantly reduce CRP in the aorta and serum.However,they cannot suppress the formation of atherosclerosis.