卡维地洛对压力负荷大鼠心室肥厚影响的实验研究

Effect of Carvedilol on Ventricular Hypertrophy in Pressure-over-loaded Rats

目的观察β受体阻滞剂卡维地洛对压力负荷大鼠心室重构的影响。方法27只雄性SD大鼠随机分为假手术组(9只)、心肌肥厚组(9只)和卡维地洛组(9只),行腹主动脉缩窄术造成后负荷增高型大鼠模型。卡维地洛组大鼠给予卡维地洛15mg/(kg·d)灌胃,心肌肥厚组和假手术组给予等量蒸馏水灌胃。4周后检测血流动力学指标和心室重量指数,采用放射免疫法测定血清TNF-α和IL-6的浓度,免疫组化法检测心室肌中MMP-2和TIMP-2的表达。结果心肌肥厚组MBP、LVESP和LVMI升高(P<0.05),血清TNF-α和IL-6水平升高(P<0.01),MMP-2和TIMP-2的表达增加(P<0.01);卡维地洛组上述指标均有所降低(P<0.05)。结论卡维地洛能减轻压力负荷大鼠的心室肥厚,下调过度表达的MMP-2及升高的TNF-α和IL-6水平是其防治心室重构的机制之一。

Objective To study the effects of carvedilol on prevention of ventricular remodeling in pressure -over- loaded rats. Methods Twenty -seven male SD rats were randomly assigned to sham - operated group （ n = 9） , hypertrophied group （ n = 9） and carvedilol group （ n = 9） . Pressure - over- loaded models were established by partial abdominal aorta ligation. Carvedilol group were treated with carvedilol 15mg/（ kg · d） by gastric larage,the other two groups were treated with the same amount of distilled water. After 4 weeks of therapy, Hemodynamic parameters and left ventricular mass index （LVMI） were detected, serum TNF -α and IL -6 levels were determined with radioimmunological assay ,and protein expression of matrix metalloproteinase - 2 （ MMP - 2） and tissue inhibitor of metalloproteinase - 2 （TIMP- 2 ） were evaluated by immunohistochemical analysis. Results Compared with the sham - group ,the MBP ,LVESP and LVMI （P 〈 0. 05 ） , the serum TNF -α and IL- 6 levels （P 〈 0. 01 ） , and the expression of MMP - 2 and TIMP - 2 （P 〈 0. 01 ） in LV increased in hypertrophied group, compared with that of the hypertrophied group,these indexes decreased in carvedilol group （P 〈 0. 01） . Conclusion Carvedilol can reverse over - expression of MMP - 2 and decrease the levels of TNF - α and IL - 6. It is one of causes of alleviating ventricular remodeling in pressure - over - loaded rats.