氯沙坦、卡托普利及联合用药对肾动脉粥样硬化的干预  

Losartan, Captopril and Combined Administration on the Treatment of Atherosclerotic Renal Vascular Disease

作　　者：谈红[1] 潘其兴[2] 梁春香[1] 魏敏[1] 克丙申[1] 尹格平[1] 罗南平[1] 丁吉元[1] 董政军[1] 

机构地区：[1]济南军区总医院,山东省济南市250031 [2]山东齐鲁医院心内科,山东省济南市250012

出　　处：《中国动脉硬化杂志》2003年第4期299-303,共5页Chinese Journal of Arteriosclerosis

基　　金：山东省科委计划课题并受全军医药卫生科研基金资助( 0 1Q0 14 )

摘　　要：为研究血管紧张素Ⅱ受体阻断剂 (氯沙坦 )和血管紧张素转化酶抑制剂 (卡托普利 )以及二者联合用药对肾动脉粥样硬化的干预 ,并进一步探讨其可能的作用机制 ,采用发色底物法测定血清一氧化氮、组织型纤溶酶原激活物、组织型纤溶酶原激活物抑制剂和血管紧张素转化酶的水平 ;用放射免疫分析法测定血浆内皮素和血管紧张素Ⅱ水平 ;用流式细胞仪检测动脉壁粥样斑块内血管平滑肌细胞增殖周期和凋亡情况 ;CD6 8蛋白表达水平检测采用免疫组织化学染色法 ;基质金属蛋白酶 1和组织型基质金属蛋白酶 1抑制物mRNA表达水平的检测采用逆转录—聚合酶链反应方法。结果发现 ,氯沙坦和卡托普利对血脂、肌酐和尿素氮水平无影响 ;氯沙坦及氯沙坦与卡托普利联合用药可显著降低动脉压 ;主动脉与肾动脉粥样硬化程度有较好的相关性 (r =0 .5 9,P <0 .0 0 1 ) ;氯沙坦组和联合服药组较高胆固醇组肾动脉内膜面积占有率显著降低 (P <0 .0 5 ) ,肾动脉胆固醇含量显著减少 (P <0 .0 5 ) ,血循环中内皮素含量明显减少 ,一氧化氮水平明显升高 (P <0 .0 1 ) ,粥样斑块中血管平滑肌细胞凋亡显著增加 (P<0 .0 1 ) ,CD6 8蛋白表达显著降低 (P <0 .0 5 ) ,基质金属蛋白酶 1mRNA表达水平显著降低 ;Aim To investigate the effects of losartan, captopril and combined administration on the atherosclerotic renal vascular disease, so as to discover the anti atherosclerotic mechanism of these two drugs. Methods Serum nitric oxide (NO), tissue plasminogen activator(t PA), inhibitor of t PA and angiotensin converting enzyme were detected by chemical method; endothelin (ET) and angiotnesin Ⅱ were detected by radioimmuno assay. The apoptosis of vascular smooth muscle cells (VSMC) was determined by cytometry technique; Expression of CD68 protein were detected by immunohistochemical method; the expression levels of MMP1 and TIMP1 mRNA were examined by reverse transcription polymerase chain reaction. Results Losartan and captopril had no influence on serum lipid, creatine and BUN. Losartan alone and combined use with captopril could lower blood pressure significantly. The degree of renal and aortic atherosclerosis had good correlation. Compared with cholesterol diet group, losartan and combined drug administration group had smaller renal intimal area ratio (P<0.05), lower cholesterol contents in the renal atherosclerotic plaque (P<0.05), higher apoptosis percentage of VSMC (P<0.01) and lower levels of the expressions of CD68 protein (P<0.05) and MMP1 mRNA. Losartan may also elevate serum content of t PA(P<0.05). Conclusions Losartan and captopril can influence the pathogenesis of renal atherosclerosis by lowering blood pressure, enhancing apoptosis of VSMC, improving endothelial function, increasing fibrolysic function and stabilizing atherosclerotic plaque.

关 键 词：内科学 药物对肾动脉粥样硬化的干预 动物实验 血管平滑肌细胞 凋亡 氯沙坦 卡托普利 

分 类 号：R54[医药卫生—心血管疾病]