卡托普利对动脉粥样硬化大鼠内皮素转换酶表达的影响  

Study of Expression and Mechanism of Endothelin-converting Enzyme in the Progression of Atherosclerosis

作　　者：徐正平[1] 朱健华[1] 邹瑞秀[1] 丁志坚[1] 蒋建光[1] 姚登福[1] 

机构地区：[1]南京医科大学附属常州第二医院,江苏常州213000

出　　处：《实用临床医药杂志》2007年第4期56-60,共5页Journal of Clinical Medicine in Practice

摘　　要：目的:观察血管紧张素转换酶抑制剂(ACEI)类药物卡托普利干预ECE-1和ECE-1mRNA的表达,探讨ACEI与内皮素(ET)系统的相互作用。方法24只雄性SD大鼠随机分为正常组、动脉粥样硬化(AS)组和卡托普利干预组;以喂高脂饮食方法建立SD大鼠AS模型,使用ACEI类药物卡托普利进行干预;在AS形成过程中,以免疫组织化学法分析各组动脉组织中ECE-1蛋白质表达与胞内定位;以半定量逆转录聚合酶链反应(RT-PCR)分析各组ECE-1mRNA表达和卡托普利干预对ECE-1mRNA表达的影响;并提取动脉血管膜,分析组织ECE-1的活性和以放射免疫法检测不同动物组血中ET-1的含量。结果正常组大鼠的内皮细胞和中膜SMC中有ECE-1微弱表达(4.32±0.05),阳性染色常位于细胞膜和胞质内;AS组大鼠的内皮细胞和内膜SMC中ECE-1表达显著增高(10.56±0.28,P<0.01)。干预鼠主要在内皮细胞和中膜SMC中表达较弱(4.54±0.13),AS鼠显著高于对照鼠和干预鼠(P<0.01)。AS鼠ECE-1mRNA表达明显高于干预组与正常组(P<0.01),表达水平分别为2.04±0.18、0.83±0.01和0.88±0.02;AS鼠ECE-1酶活性高于正常鼠和干预鼠(P<0.05);AS鼠血ET-1均值为79.42 pg/mL明显高于正常鼠32.25 pg/mL和干预鼠36.83 pg/mL(P<0.01)。结论ACEI类药物能下降血ET-1水平,可能与抑制ET-1产生的关键酶ECE-1有关,其结果有助于解析ACEI防治AS的机制。Objective To observe the effect of captopril on the expressions of ECE-1 mRNA and protein and to clarify the mechanism of ACEI reversing AS. Methods Twenty-four male SD rats were randomly divided into control group, AS group and captopril group. High lipid and FaNeng were used for inducing AS in SD rats, and other 8 rats were randomized to receive pretreated captopril. Immunohistochemistry was used to analyze the expression of ECE-1 and location in the cells; ECE-1 mRNA was detected by reverse transcription polymerase chain reaction （RT- PCR）. The changes of ECE-1mRNA expression in three groups were measured by semi-quantitative RT-PCR assays, respectively. The extracted membrane protein of artery was incubated in 100 μL assay buffer containing 0.1μmol/L big-ET-1 at 37 ℃ for 1 hour, and then the amount of Endothelin-1（ET-1） formed was analyzed by radioimmunoassay （RIA）, which represents the result of ECE-1 activity. Results Immunohistochemitstry shown in normal rat ECE-1 is weakly expressed in endothelia cells and SMC, while in AS rat its expression increased in endothelia cells and SMC, especially in paques and inflammation cells; in captopril group it was weakly expressed in endothelia cells and SMC; it was much more intense in As rat than in captopril group and normal rats . Rat ECE - 1 mRNA expression is much more intense than that of the captopril group and normal rats, too. Expression value is 2.04 ± 0.18, 0.83 ± 0.01, and 0.88 ±0.02 respectively. ECE-1 gene amplication is identical with what is expected, ECE-1 activity was hightened in SD rats with AS（P 〈 0.05）. Concentrations of serum ET-1 increased in SD rats with AS, which there were significant difference compared with control SD rats （P 〈 0.01）, respectively. Conclusion ACEI, maybe inhibit the key enzyme ECE-1, and decrease concentrations of serum ET -1. The results could throw a light on the function of ACEI reversing AS.

关 键 词：内皮素转换酶-1 动脉粥样硬化 内皮素-1 卡托普利 

分 类 号：R541.4[医药卫生—心血管疾病]