【摘要】 目的:研究运动训练联合β1肾上腺素能受体反义基因治疗对自发性高血压大鼠(SHR)血压、心功能、心脏β1受体mRNA、蛋白的影响,探讨运动训练联合β1受体反义基因治疗改善心功能的机制。方法:阳离子脂质体混合物与β1反义寡核苷酸(β1-AS-ODN)经鼠尾静脉注射,Tail-cuff法检测血压,颈动脉插管测定血流动力学指标,半定量RT-PCR测定β1mRNA水平,Western印迹测定心脏β1受体的蛋白水平。结果:与SHR组比较,运动联合基因治疗可以使血压下降维持4周,血压最大下降40mmHg,LVSP、LVEDP显著降低(P<0.01,P<0.01),左室最大收缩和舒张速率显著升高(P<0.01,P<0.01),β1受体mRNA明显降低(P<0.05),β1受体蛋白表达水平显著降低(P<0.01)。结论:运动训练联合β1受体反义基因治疗可以明显地降低血压,改善心功能;其机制是运动训练增强基因治疗对β1受体mRNA和蛋白的抑制作用,在转录和转录后抑制过度激活的β1受体的表达。更多还原

【Abstract】 Objective:To evaluate the effects of β1 adrenoreceptor antisense gene therapy on blood pressure,cardiac function,β1 adrenoreceptor mRNA and protein in spontaneously hypertensive rats SHR.Method:Liposome/AS-ODNs were tested intravenously in SHR.Blood pressure was measured by Tail-cuff method.The hemodynamic studies of the rats were performed after 4 weeks of the injection.The levels of myocardial β1 adrenoreceptor mRNA and protein were tested by RT-PCR and Western blotting.Result:On the basis of the magnitude and duration of hypotension,exercises training with β1-AS-ODN decreased blood pressure by up to 40mmHg for 4 weeks.Compared with the SHR group,after exercises training with β1-AS-ODN LVSP and LVEDP decreased(P<0.01,P<0.01) ;±dp/dtmax increased significantly(P<0.01,P<0.01) ;the levels of myocardial β1 adrenoreceptor mRNA and protein decreased significantly(P<0.05,P<0.01) .Conclusion:Exercise training with β1-AS-ODN can significantly ameliorate blood pressure and cardiac function in SHR,which is associated with reducing the levels of myocardial β1 adrenoreceptor mRNA and protein.The inhibition of overactive β1-AR expression probably occurs in transcription and post-transcriptional steps.更多还原