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目的:比较辛伐他汀早期干预与晚期干预对高血压心肌肥厚的防治效果,并初步探讨其机制。方法:采用腹主动脉缩窄法建立压力负荷高血压大鼠模型,在心肌肥厚形成的不同阶段分别给予辛伐他汀[10 mg/(kg.d),ig]干预。采用天狼猩红染色、血流动力学测定等方法,观察和比较辛伐他汀对高血压心肌肥厚和心功能的影响。应用ELISA法检测心肌组织中TNF-α、IL-6和IL-10蛋白的含量。根据Fenton反应原理应用细胞色素C还原实验测定心肌内活性氧(ROS)的水平和还原型辅酶II(NADPH)氧化酶的活性。结果:与假手术组比较,腹主动脉缩窄后8周,大鼠左室质量指数、心肌组织中胶原的含量明显升高,左室舒张功能明显下降(P<0.01)。在不同阶段给予辛伐他汀干预,均可降低左室质量和心肌中胶原的含量;与晚期干预组比较,早期辛伐他汀干预组大鼠左室质量和心肌中胶原的含量更低(P<0.05),并可提高左室舒张功能。压力负荷大鼠心肌组织内TNF-α和IL-6的水平显著升高(P<0.01),ROS的水平和氧化酶的活性亦明显升高(P<0.01);辛伐他汀干预可明显降低TNF-α、IL-6和ROS的水平以及氧化酶的活性,但与晚期干预组比较,早期辛伐他汀干预组大鼠心肌组织内TNF-α、IL-6和ROS的水平以及氧化酶的活性更低(P<0.05)。结论:在高血压的早期给予辛伐他汀干预,对高血压心肌肥厚的改善作用优于晚期药物干预,因辛伐他汀早期干预能更有效地抑制心肌组织炎性因子的表达和ROS生成。
Objective: To compare the prevention and treatment effect of simvastatin with early intervention and late intervention on hypertensive myocardial hypertrophy, and to explore its mechanism. Methods: A rat model of stress-induced hypertension was established by abdominal aorta constriction. Simvastatin [10 mg / (kg · d), ig] was administered to rats at different stages of cardiac hypertrophy. The effects of simvastatin on hypertensive cardiac hypertrophy and cardiac function were observed and compared by Sirius red staining and hemodynamics. The contents of TNF-α, IL-6 and IL-10 in myocardium were detected by ELISA. The level of reactive oxygen species (ROS) and the activity of reduced coenzyme II (NADPH) oxidase in myocardium were measured by Fenton reaction using cytochrome C reduction assay. Results: Compared with the sham group, the left ventricular mass index and the contents of collagen in myocardial tissue increased significantly and the left ventricular diastolic function decreased significantly (P <0.01) 8 weeks after abdominal aorta constriction. Simvastatin intervention at different stages decreased both left ventricular mass and collagen content in myocardium. Compared with late intervention group, left ventricular mass and myocardial collagen content in early simvastatin intervention group were lower (P < 0.05), and can improve left ventricular diastolic function. The levels of TNF-α and IL-6 were significantly increased (P <0.01), the level of ROS and the activity of oxidase were significantly increased in stress-loaded rats (P <0.01), and the intervention with simvastatin was significantly decreased TNF-α, IL-6 and ROS levels and oxidase activity, but compared with the late intervention group, the levels of TNF-α, IL-6 and ROS in the myocardium of the early simvastatin intervention group Less active (P <0.05). Conclusion: Simvastatin intervention in the early stage of hypertension can improve myocardial hypertrophy better than that of late drug intervention. Early intervention with simvastatin can inhibit the expression of myocardial inflammatory cytokines and ROS more effectively.