摘要
目的观察阿托伐他汀对自发性高血压大鼠(SHR)心肌中过氧化物酶体增殖物激活受体γ(PPARγ)及葡萄糖转运蛋白4(GLUT4)表达的影响,探讨阿托伐他汀改善SHR左心室肥厚的可能机制。方法 16只SHR随机分为高血压模型组(n=8)与阿托伐他汀组(n=8),8只Wistar-Kyoto(WKY)大鼠作为正常血压对照(WKY组),阿托伐他汀组按阿托伐他汀50mg/(kg·d)标准予以灌胃,WKY组与高血压模型组均予以等容量蒸馏水灌胃。每隔2周测1次血压。10周末处死,测血脂,计算左心室质量指数(LVMI=左心室质量/体质量)。HE染色观察心肌组织形态,免疫组化法及RT-PCR法检测大鼠心肌组织PPARγ、GLUT4的表达。结果高血压模型组LVMI高于WKY组[(3.77±0.47)比(2.85±0.18)mg/g,P<0.05],高血压模型组心肌组织中PPARγ、GLUT4的表达水平低于WKY组(PPARγ:1.15±0.02比1.23±0.03;GLUT4:1.07±0.08比1.21±0.06,均P<0.05);经阿托伐他汀干预后,阿托伐他汀组高血压大鼠LVMI低于高血压模型组[(3.26±0.29)比(3.77±0.47)mg/g,P<0.05],阿托伐他汀组PPARγ、GLUT4高于高血压模型组(PPARγ:1.19±0.04比1.15±0.02,GLUT4:1.13±0.03比1.07±0.08,均P<0.05);阿托伐他汀干预前后,SHR血压、血脂水平差异无统计学意义(均P>0.05)。结论阿托伐他汀具有调脂作用以外的抑制高血压左心室肥厚的作用,其机制可能与上调肥厚心肌组织中PPARγ、GLUT4的表达有关。
Objective To investigate the effects of atorvastatin on the expressions of peroxisome proliferator-activated receptoγ(PPARy) and glucose transporter-4 (GLUT4)in the myocardium of spontaneously hypertensive rats (SHR), and to study the possible mechanisms for atorvastatin to attenuate left ventricular hypertrophy. Methods A total of sixteen SHR were randomly divided into hypertensive group (n = 8 ) and atorvastatin group ( n = 8 ). Eight age matched WKY were chosen as control group (WKY group, n= 8). A dose of 50 mg/kg atorvastatin was given to atorvastatin group per day by gastric gavage, and the same volume of distilled water was given to WKY group and hypertensive group. The blood pressure was measured every two weeks. All the rats were put to death at the end of the 10th week. The fasting serum lipid was detected, the ratio of left ventricular mass index (LVMI) calculated, myocardial tissue morphology observed by HE-staining, and the expressions of PPAR7 and GLUT4 in the myocardium tested by immunohistochemistry analysis and RT-PCR. Results The LVMI in hypertensive group was significantly higher than in WKY group [(3.77±0.47) vs (2. 85±0.18)mg/g, P〈0. 051, and the expressions of PPAR7 and GLUT4 in the myocardium were statistically lower in hypertensive group compared with those in WKY group [PPARγ: (1. 15±0.02) vs (1.23±0.03), P〈0.05; GLUT4: (1.07±0.08) vs (1.21±0.06), all P〈0.05]. After the intervention of atorvastatin, the LVMI in atorvastatin group was lower than in hypertensive group [(3. 26±0.29) vs (3.77±0.47)mg/g, P〈0.05), and the expressions of PPARy and GLUT4 in atorvastatin group were higher compared with those in hypertensive group [PPARγ: (1.19±0.04) vs (1.15±0.02), P〈0.05; GLUT4: (1. 13±0.03) vs (1.07±0.08), P〈0.05], but there was no statistically significant difference in blood pressure and serum lipid levels between hypertensive group and atorvastatin group (P〉0.05). Conclusion Atorvastatin regulates blood lipid and ameliorates left ventricular hypertrophy in hypertension, which may be related with the up-regulation of PPARγ and GLUT4 levels in hypertrophic myocardium.
出处
《中华高血压杂志》
CAS
CSCD
北大核心
2013年第6期542-547,共6页
Chinese Journal of Hypertension
基金
川北医学院苗圃基金(MP-ZK-24)