【摘要】 目的 观察吡咯烷二硫基甲酸盐(PDTC)对心肌肥大发生发展的影响并探讨其机制。方法 以缩窄小鼠主动脉弓(TAC)诱导的心肌肥大为模型，观察PDTC对心肌肥大发生发展的影响，并采用EMSA检测心肌组织中NF-κB结合活性，应用Western blot方法分析心肌组织中phospho-GSK3β的表达水平。结果 (1)缩窄小鼠主动脉弓2周后，心脏重量/体重比值与假手术组相比增高48.7% (P<0.01)，而且肥大心肌组织中NF-κB结合活性和phospho-GSK3β(Ser9)蛋白表达明显高于假手术组(P<0.01)。(2)PDTC可明显减轻TAC诱导的心肌肥大，与TAC模型组相比可以使小鼠心脏重量/体重比值下降16.4%(P<0.05)。PDTC可抑制心肌组织中NF-κB活性，与TAC模型组相比降低了34.3%(P<0.01)，同时亦可抑制心肌组织中GSK3β(Ser9)磷酸化水平，p-GSK3β(Ser9)/ GSK3β比TAC模型组降低了22.1%(P<0.05)。结论 PDTC可以通过抑制NF-κB结合活性和GSK3β(Ser9)磷酸化水平延缓心肌肥大的发生发展。

    【关键词】 心肌肥大；吡咯烷二硫基甲酸盐；核因子κB; 糖原合成激酶-3β

    The preventive effect and mechanism of PDTC on the development of mice cardiac hypertrophy induced by pressure overload

    LI Yue-hua,LI Jing,QUE Ling-Li.

    Department of Pathophysiology,Nanjing Medical University,Najing 210029,China

    【Abstract】 Objective To investigate the role and mechanism of PDTC on the development of cardiac hypertrophy in vivo.Methods PVB/N mice were employed and cardiac hypertrophy was induced by transverse aortic constriction for 2 weeks.Electrophoretic mobility shift assay (EMSA) was used to determine NFkB binding activity with nuclear proteins extracted from heart tissues; Western blots were performed to examine the phosphorylation of GSK-3β. In a separate experiment, PDTC was administered into mice subjected to transverse aortic constriction for 2 weeks.Results (1)Transverse aortic constriction(TAC) significantly increased the ratio of HW/BW. Two weeks after TAC, the ratio of HW/BW was significantly increased by 48.7%(P<0.01), compared to age-matched sham control. NFkB binding activity and the level of phospho- GSK-3β(Ser9) were significantly increased at 2 weeks following TAC compared to age-matched sham control (P<0.01).(2)Administration of PDTC into TAC mice for 2 weeks, significantly reduced the ratio of HW/BW by 16.4%(P<0.05), compared to non-treated TAC mice. NFkB binding activity was significantly reduced by 34.3% (P<0.01) in the hearts administered with PDTC for 2 weeks, compared to non-treated TAC group. In addition,administration of PDTC also decreased the level of phospho- GSK-3β(Ser9)/ GSK-3β by 22.1%(P<0.05) compared to non-treated TAC group.Conclusion PDTC inhibit the NFkB binding activity and the level of phospho- GSK-3β(Ser9) in hypertrophic heart tissues and thereby attenuates the development of cardiac hypertrophy. ......