奥美沙坦酯对慢性心力衰竭小鼠的保护作用

目的:观察奥美沙坦酯对慢性心力衰竭小鼠的保护作用。方法:健康C57小鼠随机分为假手术组(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OLM组以10mg/kg剂量每日胃饲,4周时观察各组小鼠心率、血压及一般状况,检测血浆和心脏血管紧张素(Ang)Ⅱ水平;Real-timePCR法检测心脏血管紧张素Ⅱ1型受体(AT1R)、Ⅰ型胶原、Ⅲ型胶原的表达情况,AZAN染色观察心脏组织结构变化。结果:与SHAM组相比,CHF组收缩压显著增高,OLM组较CHF组显著降低(P<0.05)。与SHAM组相比,CHF组血浆和心脏AngⅡ水平,AT1R和Ⅰ、Ⅲ型胶原的表达增高(P<0.05),OLM组心脏AngⅡ水平,AT1R和Ⅰ、Ⅲ型胶原的表达较CHF组均明显降低(P<0.05)。CHF组AZAN染色可见心肌组织中梗死区蓝染,心肌纤维消失,代之以纤维结缔组织,OLM组亦可见蓝染的纤维结缔组织,但与CHF组相比面积减少。结论:慢性心力衰竭可使心内肾素血管紧张素系统激活并导致心脏损伤,奥美沙坦酯通过抑制AngⅡ起到保护心脏作用。

The Protective Effect of Olmesartan Medoxomil on Chronic Heart Failure in Mice

Objective:To investigate the protective effect of olmesartan medoxomil(OLM) on chronic heart failure(CHF) in mice.Methods:C57 mice were divided into sham operation group(SHAM group),chronic heart failure group(CHF group) and olmesartan medoxomil treatment group(OLM group).The experimental CHF model was established by coronary artery ligation.Mice of OLM group were fed with OLM at daily dose of 10 mg/kg.The heart rate,blood pressure,plasma and cardiac angiotensin Ⅱ levels were observed after four-week treatment.The cardiac angiotensin Ⅱ type 1 receptor(AT1R),expressions of type Ⅰand type Ⅲ collagen were detected by real-time PCR.The cardiac pathological changes were determined by AZAN staining.Results:Compared with SHAM group,the systolic blood pressure,plasma and cardiac angiotensin Ⅱ levels,AT1R and typeⅠand Ⅲ collagen expression were significantly increased in CHF group(P < 0.05),while in OLM group,they were significantly lower than those in CHF group except for the plasma angiotensin Ⅱ level(P < 0.05).AZAN stain showed that blue-stained myocardial infarction was in CHF group,the myocardial fibers were disappear and replaced by fibrous connective tissue.There was blue-stained fibrous connective tissues in OLM group,but the area was reduced compared with that of CHF group.Conclusion:Chronic heart failure can activate the intracardiac renin-angiotensin system,leading to heart damage.Olmesartan medoxomil can protect heart by inhibiting effects of angiotensin Ⅱ.