奥美沙坦酯对慢性心力衰竭小鼠肾脏氧化应激的作用

目的 探讨奥美沙坦酯对慢性心力衰竭小鼠肾脏氧化应激的作用。 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剂量每日胃饲,12周时观察各组小鼠心率、血压、心功能状况、Scr、BUN、血浆和肾脏血管紧张素（Ang）Ⅱ水平。实时PCR法检测肾脏gp91phox、p22phox和NOX4的表达。AZAN染色和二氢乙啶（DHE）染色观察肾组织病理变化。 结果 与SHAM组比较,CHF组和OLM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）;CHF组收缩压、Scr和BUN显著增高,而OLM组以上指标较CHF组均显著降低（P ＜ 0.05）。与SHAM组比较,CHF组血浆和肾脏AngⅡ水平增高,gp91phox、p22phox和NOX4表达增高（P ＜ 0.05）;OLM组肾脏AngⅡ水平、gp91phox、p22phox和NOX4表达较CHF组均显著降低（P ＜ 0.05）。与SHAM组比较,CHF组肾脏AZAN染色和DHE染色阳性增强（P ＜ 0.05）,而OLM组较CHF组显著降低（P ＜ 0.05）。 结论 慢性心力衰竭可使肾内NADPH氧化酶激活并导致肾小球间质纤维化,奥美沙坦酯通过抑制AngⅡ引起的氧化应激反应起到肾脏保护作用。

Effect of olmesartan medoxomil on renal oxidative stress in mice with chronic heart failure

Objective To investigate the effect of olmesartan medoxomil on renal oxidative stress in mice with chronic heart failure. Methods C57 mice were divided into sham operation group(SHAM group),chronic heart failure group(CHF group)and olmesartan medoxomil treatment group(OLM group).Experimental CHF model was established by coronary artery ligation,in which OLM group fed with a daily dose of 10 mg/kg.The heart rate,blood pressure,cardiac function,Scr,BUN,and plasma and kidney angiotensin(Ang)Ⅱ were measured.Real-time PCR was used to examine renal gp91phox,p22phox and NOX4 expression.AZAN and DHE staining was used to detect renal pathological change after 12 weeks. 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 CHF and OLM groups (P<0.05).Compared with SHAM group,systolic blood pressure,Scr,BUN,and AZAN and DHE staining positive area were significantly increased in CHF group(P<0.05),while above indexes were significantly lower in OLM group as compared to CHF group(P<0.05).Compared with SHAM group,plasma and kidney Ang Ⅱ levels,gp91phox,p22phox and NOX4 expression were increased in CHF group(P<0.05),while above indexes were significantly lower in OLM group as compared to CHF group (P<0.05).Conclusions Chronic heart failure can activate intrarenal NADPH oxidase resulting in renal injury.Olmesartan medoxomil can protect kidney by inhibiting the effect of Ang Ⅱ-induced oxidative stress.