卡托普利对兔动脉粥样硬化斑块局部C反应蛋白表达的影响

The effects of captopril on the expressions of C-reactive protein in the aortic plaques of atherosclerotic rabbits

目的通过建立兔动脉粥样硬化(AS)模型,观察斑块局部C反应蛋白(CRP)的水平,并观察卡托普利对CRP的影响作用,探讨卡托普利除了抗高血压作用外对血管局部炎症反应的影响。方法雄性健康新西兰兔22只,随机分为3组:①高脂饮食组8只,给予含1%胆固醇+4%猪油饲料;②高脂饮食加卡托普利组8只,饲以1%胆固醇+4%猪油饲料+卡托普利(2mg·kg-1·d-1);③正常对照组6只,饲以标准兔饲料,各组均喂养10周。实验结束后,测各只动物血浆血管紧张素Ⅱ(AngⅡ)水平及血脂;并取主动脉组织作形态学观察并做CRP免疫组织化学分析。结果①高脂饮食组血浆AngⅡ含量与正常对照组相比明显升高[(1597±116)pg/mlvs(86±6)pg/ml,P<0.01];高脂饮食加卡托普利组AngⅡ水平较高脂饮食组明显下降,但仍高于正常对照组[分别为(386±57)pg/mlvs(1597±116)pg/ml,P<0.01;(386±57)pg/mlvs(86±6)pg/ml,P<0.01];②高脂饮食组斑块局部CRP表达较对照组显著增高[(42.1±11.6)%vs(1.8±0.5)%,P<0.01],卡托普利组较高脂饮食组明显下降[(23.6±5.3)%vs(42.1±11.6)%,P<0.01];③在卡托普利的干预下,血浆AngⅡ的水平与斑块局部的CRP的表达呈正相关(t=0.673,P<0.01)。结论①卡托普利明显降低斑块局部CRP的表达,减轻斑块局部的炎症反应;②血浆中AngⅡ与AS斑块中CRP的表达呈正相关。

Objective To observe the level of plasma angiotensin Ⅱ （AngⅡ） and local expression of C- reactive protein （CRP） in aortic plaques of atherosclerotic rabbits after intervention by eaptopfil, and to elucidate the anti-inflammatory effects of captopril in addition to antihypertensive action. Methods Twenty-two male rabbits were randomized into three groups： ①high-fat diet group, given 1% cholesterol and 4% lard （n=8）; ②captopril treated high-fat diet group, given 1% cholesterol and 4% lard and treated with 2 mg·kg^-1·d^-1 captopril （n=8）; ③control group, given standardized rabbit food （n=6）. After 10 weeks, the levels of plasma Ang Ⅱ and lipids were measured by radioimmuoassay, and the aortas were harvested for pathological study and measurement of CRP by immunohistochemistry. Results ①Compared with control group, the level of plasma Ang Ⅱ was significantly increased in high-fat diet group [（1597±116） pg/ml vs （86±6）pg/ml, P〈0.01 ]. In captopril-treated highfat diet group, the level of plasma Ang Ⅱ was decreased significantly than that of high-fat diet group [（386±57） pg/ml vs （1597±116） pg/ml,P〈0.01 ], but was nevertheless significantly higher than that of control group [（386± 57） pg/ml vs （86±6）pg/ml, P〈0.01 ]. ②Compared with control group, the percentage of CRP-positive cells in plaques were significantly increased in high-fat diet group [ （42.1 ± 11.6） % vs （ 1.8 ±0.5 ） %, P〈0.01 ]. Captopril dramatically reduced the percentage of CRP-positive cells in plaques [（23±5）% vs （42±12）%,P〈0.01 ]. ③Plasma Ang Ⅱ was positively correlated with the expression of CRP in local atherosclerotie plaques （t=0.673, P〈 0.01 ）. Conclusion Captopril can reduce the expression of CRP in local plaques of aortic atherosclerosis, and suppress vascular inflammation. Plasma Ang Ⅱ was positively correlated with the expression of CRP in atherosehrotic plaques.