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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 ;氯沙坦还可显著升高组织型纤溶酶原激活物水平
In order to study the intervention of angiotensin Ⅱ receptor blockers (losartan) and angiotensin converting enzyme inhibitors (captopril) and their combination therapy on renal atherosclerosis and to explore its possible The mechanism of action, using chromogenic substrate method for the determination of serum nitric oxide, tissue-type plasminogen activator, tissue-type plasminogen activator inhibitor and angiotensin converting enzyme levels; radioimmunoassay Endothelin and angiotensin Ⅱ levels. Flow cytometry was used to detect the proliferation and apoptosis of vascular smooth muscle cells in atherosclerotic plaque. The expression of CD68 protein was detected by immunohistochemical staining. The expressions of matrix metalloproteinase 1 Tissue matrix metalloproteinase 1 inhibitor mRNA expression levels using reverse transcription - polymerase chain reaction method. The results showed that losartan and captopril had no effect on serum lipids, creatinine and urea nitrogen; losartan and losartan combined with captopril significantly reduced arterial pressure; aortic and renal atherosclerosis (R = 0.59, P <0.01). The intima area of renal artery in losartan group and the combination group with high cholesterol group was significantly lower (r = 0.59, P < (P <0.05). The content of endothelin in the blood circulation was significantly decreased, the level of nitric oxide was significantly increased (P <0.01), the content of vascular smooth muscle in atherosclerotic plaque (P <0.01), CD6 8 protein expression was significantly lower (P <0.05), and MMP-1 mRNA expression was significantly lower; Losartan also significantly increased tissue fibrinolysis Enzyme activator levels