奥美沙坦不依赖血管紧张素Ⅱ改善压力超负荷诱发的小鼠心脏肥大

Olmesartan Regresses Pressure Overload-Induced but Angiotensin Ⅱ-Independent Cardiac Hypertrophy in Mice

目的探讨奥美沙坦在无内源性血管紧张素II(AngII)情况下能否抑制压力超负荷导致的小鼠心脏肥厚。方法通过缩窄升主动脉(TAC)构建小鼠压力超负荷心脏肥大模型。8-10周龄野生型(WT)和血管紧张素原基因敲除(ATGKO)小鼠各随机分为3组:假手术组,生理盐水组和奥美沙坦组。TAC两周后,对小鼠心脏进行超声及病理形态学检测,同时测量左心室压力、全心/体重比值以及相关肥大基因检测。结果相对于假手术组,生理盐水组心脏肥厚各项指标值明显变大(P<0.05)。奥美沙坦组心脏肥厚的各项指标值均显著低于生理盐水组(P<0.05);在WT小鼠和ATGKO小鼠可见相似结果。结论奥美沙坦在无内源性AngII的条件下也能有效抑制压力超负荷所致心肌肥厚,其作用机制可能是不依赖于AngII而直接抑制压力超负荷触发的AT1受体的活化。

Objective This study is designated to investigate whether Olmesartan regresses cardiac hypertrophy induced by pressure overload in the absence of endogenous angiotensin II（AngII） in mice.Methods Constricting transverse aorta（TAC） were used as a model for pressure-overload cardiac hypertrophy.Wild Type（WT） C57BL/6J and angiotensinogen-deficient（ATG KO） mice of 8-10 weeks were divided into three groups,respectively：Sham-operated group（Sham）,TAC plus Saline group（Saline） and TAC plus Olmesartan group（Olmesartan）.After 2 weeks of TAC,echocardiography assessments were performed for the geometry and functions of hearts,and then mice were subjected to catheterization to measure the left ventricular pressure.Cardiac hypertrophy was confirmed further by histological analysis.The expressions of special genes associated with cardiac hypertrophy were determined by Real-time PCR.Results Compared to Sham group,all the values of cardiac hypertrophic index for Saline group increased signif icantly（P0.05）;Olmesartan can markedly abolish the increased cardiac hypertrophy and signif icantly inhibit the upregulation of special gene expressions induced by pressure overload,compared with Saline group（P0.05）.The result is similar regardless of whether in WT or ATG KO mice.Conclusions Omlesartan can abrogate pressure overload-induced cardiac hypertrophy even in the absence of endogenous AngII,and the underlying mechanisms may be that Olmesartan inhibited activation of AT1 receptor induced by pressure overload independent of AngII.