奥美沙坦酯对自发性高血压大鼠心室重构的影响

Effect of olmesartan medoxomil on ventricular remodeling in spontaneously hypertensive rats

目的研究奥美沙坦酯对自发性高血压大鼠(SHR)心室重构及过氧化物酶体增殖物激活受体α(PPARα)、过氧化物酶体增殖物激活受体γ(PPARγ)表达的影响。方法将36只雄性SHR随机分为模型组与实验组,各18只;同时选择18只相应周龄的Wistar Kyoto(WKY)大鼠作为对照组。实验组大鼠灌胃给予奥美沙坦酯10 mg·kg^(-1)·d^(-1),对照组与模型组均灌胃给予等量生理盐水,每天1次,均连续灌胃4周。用心脏彩色多普勒超声仪检测舒张末期室间隔厚度(IVSd)、收缩末期室间隔厚度(IVSs)、左心室舒张末期后壁厚度(LVPWd)、左心室收缩末期后壁厚度(LVPWs)与心率(HR);用苏木精-伊红(HE)染色观察大鼠心肌组织病理学变化;用放射免疫法测定血浆内皮素(ET)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)与肾素活性(PRA)含量;用蛋白质印迹(Wb)法检测心肌组织PPARα和PPARγ蛋白表达。结果对照组、模型组与实验组大鼠IVSd分别为(1.18±0.07),(3.14±0.25)和(2.21±0.19)mm;IVSs分别为(2.06±0.19),(4.19±0.36)和(3.13±0.27)mm;LVPWd分别为(1.38±0.16),(3.07±0.23)和(2.41±0.20)mm;LVPWs分别为(2.14±0.26),(4.12±0.35)和(2.98±0.31)mm;HR分别为(216.42±24.83),(425.11±46.02)和(234.69±26.15)次/分。与对照组比较,模型组大鼠IVSd、IVSs、LVPWd、LVPWs与HR及血浆ET、AngⅡ、ALD、PRA含量均显著升高,且实验组均显著低于模型组;而模型组心肌组织PPARα、PPARγ蛋白相对表达量均显著低于对照组,实验组均显著高于模型组(均P<0.05)。结论奥美沙坦酯可有效改善SHR心脏结构,同时可通过上调心肌组织PPARα和PPARγ蛋白表达,抑制心室重构,改善心脏功能。

Objective To investigate the effects of olmesartan medoxomil on ventricular remodeling and expression of peroxisome proliferator activated receptorα(PPARα),peroxisome proliferator activated receptorγ(PPARγ)in spontaneously hypertensive rats.Methods Thirty-six male SHRs were randomly divided into model group(n=18)and test group(n=18);and 18 Wistar Kyoto(WKY)rats of corresponding age were selected as control group.Rats in test group were given olmesartan medoxomil 10 mg·kg^(-1)·d^(-1) by gavage,control group and model group were given the same amount of normal saline,once a day by gavage,for 4 weeks.The interventricular septal thickness at diastole(IVSd),interventricular septum systole(IVSs),left ventricular posterior wall diastolic thickness(LVPWd),left ventricular posterior wall at end systolic(LVPWs)and heart rate(HR)were detected by color doppler ultrasound;hematoxylin-eosin(HE)staining was used to observe the pathological changes of rat myocardium tissues;the content of plasma endothelin(ET),angiotensinⅡ(AngⅡ),aldosterone(ALD)and plasma renin activity(PRA)were determined by radioimmunoassay;Western blotting(Wb)method was used to detect the protein expression of PPARαand PPARγin myocardium tissues.Results The IVSd in control group,model group and test group were(1.18±0.07),(3.14±0.25),(2.21±0.19)mm;IVSs were(2.06±0.19),(4.19±0.36),(3.13±0.27)mm;LVPWd were(1.38±0.16),(3.07±0.23),(2.41±0.20)mm;LVPWs were(2.14±0.26),(4.12±0.35),(2.98±0.31)mm;HR were(216.42±24.83),(425.11±46.02),(234.69±26.15)time·min^(-1).Compared with control group,the IVSd,IVSs,LVPWd,LVPWs and HR,plasma ET,AngⅡ,ALD and PRA contents in model group were significantly increased,and test group were lower than model group;the relative expression levels of PPARαand PPARγprotein in model group were lower than those in control group,and test group were higher than model group(all P<0.05).Conclusion Olmesartan medoxomil can effectively improve the heart structure of SHR,and it can inhibit the ventricular remodeling and improve cardiac function by up-regulating the expression of PPARαand PPARγprotein in myocardial tissue.