瑞舒伐他汀对大鼠肥厚心肌组织PPARγ和NF-κB蛋白表达的影响

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目的探讨瑞舒伐他汀对异丙肾上腺素(isoproterenol,Iso)诱导心肌肥厚大鼠心肌组织PPARγ和NF-κB表达的影响及其抑制心肌肥厚,改善心功能的机制。方法 40只雄性SD大鼠随机分为4组:正常对照组、模型组、瑞舒伐他汀组和卡托普利组,每组10只。除正常对照组外,各组背部皮下注射Iso建立心肌肥厚模型。模型制备成功后,瑞舒伐他汀组灌胃给予瑞舒伐他汀4 mg.kg-1.d-1,卡托普利组灌胃给予卡托普利50 mg.kg-1.d-1,其余两组灌胃给予等体积生理盐水。4 w末,分别测定各组大鼠左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室压力上升及下降最大速率(±dp/dt max);测定大鼠体重(BW)、心脏重量(HW)及左心室重量(LVW),计算心脏重量指数(HWI)及左心室重量指数(LVWI);应用病理学方法观察心肌组织形态学改变;Western印迹法测定心肌组织PPARγ和NF-κB亚基p65蛋白表达。结果模型组大鼠LVEDP、HWI、LVWI明显高于正常对照组(P<0.01),LVSP和±dp/dt max明显降低(P<0.01);模型组PPARγ表达明显低于正常对照组(P<0.01),p65表达明显升高(P<0.01);瑞舒伐他汀组和卡托普利组PPARγ表达明显高于模型组(P<0.01),p65表达明显降低(P<0.01);瑞舒伐他汀组和卡托普利组比较,上述指标差异均无统计学意义(P>0.05)。结论瑞舒伐他汀抑制心肌肥厚,改善心功能,其机制与增加PPARγ表达,降低p65表达有关。 Objective To investigate the effect of rosuvastatin on the expression of PPARγ and NF-κB in myocardium of rats with myocardial hypertrophy induced by isoproterenol (Iso) and its mechanism of inhibiting cardiac hypertrophy and improving cardiac function. Methods Forty male SD rats were randomly divided into 4 groups: normal control group, model group, rosuvastatin group and captopril group, with 10 rats in each group. In addition to the normal control group, each group injected subcutaneously with Iso to establish a model of cardiac hypertrophy. After the successful preparation of the model, rosuvastatin group was orally administered with rosuvastatin 4 mg.kg-1.d-1, captopril group was given captopril 50 mg.kg-1.d-1 The other two groups were given equal volume of normal saline. At the end of 4 weeks, the left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), left ventricular pressure and maximum descending rate (± dp / dt max) , Heart weight (HW) and left ventricular weight (LVW) were calculated. Cardiac weight index (HWI) and left ventricular mass index (LVWI) were calculated. Morphological changes of myocardium were observed by histopathology. -κB subunit p65 protein expression. Results The LVEDP, HWI and LVWI in model group were significantly higher than those in normal control group (P <0.01), and LVSP and ± dp / dt max were significantly decreased (P <0.01). The PPARγ expression in model group was significantly lower than that in normal control group (P < 0.01). The expression of p65 in rosuvastatin group and captopril group was significantly higher than that in model group (P <0.01), while the expression of p65 was significantly lower (P <0.01) There was no significant difference between the statins and the captopril group (P> 0.05). Conclusion Rosuvastatin can inhibit cardiac hypertrophy and improve cardiac function. Its mechanism is related to increasing PPARγ expression and decreasing p65 expression.
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