AIM: To investigate the protective effect of olmesartan medoxomil on renal injury in mice with chronic heart failure ( CHF ).METHODS : C57 mice were divided into sham operation group ( sham group ), chronic heart failure group ( CHF group ) and olmesartan medoxomil treatment group ( OLM + CHF group ).The experimental CHF model was established by ligation of left anterior descending branch of coronary artery.The mice in OLM + CHF group were fed with olmesartan medoxomil daily at the dose of 10 mg/kg.After 12 weeks, the heart rate, blood pressure, cardiac functions, serum creatinine and blood urea nitrogen levels, the angiotensin Ⅱ levels in plasma and renal tissues were measured.The expression levels of renal rennin, angiotensin type Ⅰ receptor( AT1R ) and angiotensinogen ( AGT ) were determined hy real - time PCR.The pathological changes of the kidneys were observed under microscope with PAS staining.RESULTS : Compared with sham group, left ventricular end - diastolic dimension( LVDd ) and left ventricular end - systolic dimension( LVDs ) were significantly increased ( P ＜ 0.05 ), while fractional shortening( FS ) and ejection fraction( EF )were significantly decreased in the mice of CHF and OLM + CHF groups ( P ＜ 0.05 ).Compared with sham group, systolic blood pressure, the levels of serum creatinine and blood urea nitrogen, and the PAS staining positive area of the kidneys were significantly increased in CHF group ( P ＜ 0.05 ), while in OLM + CHF group these changes were significantly lower than those in CHF group ( P ＜ 0.05 ).Compared with sham group, the levels of angiotensin Ⅱ in plasma and kidney, the expression of renin, ATIR and AGT were increased in CHF group ( P ＜ 0.05 ).In ()LM + CHF group, the angiotensin Ⅱlevel in the kidneys and the expression of renin, AT1R and AGT were significantly lower than those in CHF group ( P ＜0.05 ).CONCLUSION: Chronic heart failure activates the intrarenal renin - angiotensin system, leading to glomerular sclerosis and renal injury.Olmesartan medoxomil protects kidneys by inhibiting the effects of angiotensin Ⅱ .%目的:探讨奥美沙坦酯对慢性心力衰竭小鼠肾脏损伤的影响.方法:健康C57小鼠分为假手术组(sham组)、慢性心力衰竭组(CHF组)和奥美沙坦酯治疗组(OLM+CHF组).以冠状动脉左前降支结扎法建立慢性心力衰竭小鼠模型,其中奥美沙坦酯治疗组以10 mg/kg剂量每天胃饲.12周时观察各组小鼠心率、血压、心功能状况、血肌酐、血尿素氮、血浆和肾脏血管紧张素Ⅱ水平;real-time PCR法检测肾脏肾素、血管紧张素1型受体(AT1R)和血管紧张素原(AGT)的表达情况,PAS染色观察肾组织结构变化.结果:与shan组相比,CHF组和OLM+CHF组左室舒张末期内径(LVDd)和左室收缩末期内径(LVDs)显著增加(P＜0.05),短轴缩短率(FS)和射血分数(EF)显著降低(P＜0.05).与sham组相比,CHF组收缩压、血肌酐和血尿素氮含量显著增高,OLM+CHF组以上指标较CHF组均显著降低(P＜0.05).与sham组相比,CHF组血浆和肾脏血管紧张素Ⅱ水平增高,肾素、AT1R和AGT表达增高(P＜0.05),OLM+CHF组肾脏血管紧张素Ⅱ水平、肾素、AT1R和AGT表达较CHF组均显著降低(P＜0.05).CHF组PAS染色可见肾小球系膜区扩张,肾小管间质PAS阳性染色物明显增多.OLM+CHF组肾小球系膜区和肾小管间质PAS染色阳性物质与CHF组相比明显减少.结论:慢性心力衰竭可使肾内肾素血管紧张素系统激活并导致肾脏损伤,奥美沙坦酯通过抑制血管紧张素Ⅱ起到肾脏保护作用.
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