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β1肾上腺素受体反义寡核苷酸治疗对肾性高血压大鼠心肌一氧化氮合成酶及凋亡的影响
Effects of Antisense oligodeoxynucletide on Cardiomyocyte Apoptosis and Expression of Inducible Nitric Oxide Synthase in 2K1C Renal Hypertension Rats
【摘要】 目的探讨阳离子脂质体作为载体的β1肾上腺素受体反义寡核苷酸治疗肾性高血压大鼠降压的机制及对心脏重塑的作用,探讨高血压治疗的新方法。方法建立两肾一夹肾性高血压大鼠模型后随机分成A至D组,其中A组给予反义基因治疗(0.5mg/kg,造模后9周,1次),B组给予反向序列作对照(0.5mg/kg,造模后9周,1次),C组口服卡维地洛(1mg/kg·d,1月),D组不施加干预,E组为假手术组,F组为正常对照。心肌细胞凋亡检测采用TdT介导的原位末端缺口标记法(TUNEL),iNOS的检测采用免疫组化SP法。结果与B组、D组相比,A组血压明显降低,凋亡细胞数量明显减少,iNOS的阳性表达率明显下降(P<0.01),并且高于正常组及假手术组(P<0.05)。结论以阳离子脂质体为载体的β1肾上腺素受体反义寡核苷酸治疗可以降低血压,抑制心肌细胞凋亡,降低iNOS的含量,达到了对靶器官的保护作用,延缓了心衰。
【Abstract】 Objective To explore the anti-hypertension and anti-apoptosis effect of the antisense oligodeoxynucletide of β1 -adrenergic receptor in 2K1C renal hypertensive rats. Methods Twenty-four SD rats were divided into 4 groups, 6 rats each. Rats in group A were injected with antisense oligodeoxynucletide of 0. 5 mg/kg once. Group B were injected with inverted antisense oligodeoxynucletide of 0. 5 mg/kg once. Group C were fed with carvedilol of 1. 0 mg/kg·d for one month Apoptosis were detected by TUNEL. The content of iNOS were detected by SP. Results BP was reduced markedly(P<0. 01) in groups injected with antisense oligodeoxynucletide and fed with carvedilol along with decreases in left ventricular weight/body weight index (P<0. 01 ). Antisense oligodeoxynucletide decrease aptoptosis index and the content of iNOS in cardiomyocytes compared with 2K1C control and inverted antisense oligodeoxynuclletide groups. Conclusion Antisense oligodeoxynucletide reduces blood pressure, attenuates apoptosis of cardiomyocyte and delays the development of heart failure in 2K1C renal hypertensive rats.
【Key words】 β1 -adrenergic receptor; Antisense oligodeoxynucletide; Cardiomyocyte apoto- sis; Rat; Hypertension; iNOS;
- 【文献出处】 高血压杂志 ,Chinese Journal of Hypertension , 编辑部邮箱 ,2005年02期
- 【分类号】R544.1
- 【被引频次】5
- 【下载频次】121