【摘要】 目的 :观察阳离子脂质体 (DOTAP DOPE)介导的 β1肾上腺素能受体mRNA反义寡核苷酸 (β1 AS ODN)对肾性高血压大鼠血流动力学及心肌肥厚的影响。方法 :建立二肾一夹 (2K1C)肾性高血压大鼠模型 ,随机分为假手术组、模型组、反向寡核苷酸组、反义寡核苷酸组和卡维地洛 (carvedilol)组。ODN与DOTAP DOPE以 1 2摩尔比混合 ,4周末尾静脉注射 0 .5mg·kg-1,卡维地洛 10mg·kg-1·d-1灌胃 4周。定期测血压 ,8周末测血流动力学参数 ,左室重量指数 (LVWI)及血浆内皮素 1(ET 1)浓度 ,并对LVWI与ET 1进行线性相关分析。结果 :与反向寡核苷酸组比 ,β1 AS ODN能降低血压最高达39mmHg并持续 2 7d(30 .4 4± 6 .5 0 ,P <0 .0 1) ,降低左室收缩压 (LVSP) (P <0 .0 5 )、左室舒张末压 (LV EDP) (P <0 .0 1) ,升高左室最大收缩和舒张速率 (±dp dtmax) (P <0 .0 1) ,降低LVWI(P <0 .0 5 )及血浆ET 1(P <0 .0 1) ;与卡维地洛组比 ,各指标均无显著性差异。LVWI与ET 1显著正相关 (r =0 .74 9,P <0 .0 1)。结论 :DOTAP DOPE介导的 β1 AS ODN单剂量静脉注射能持续降压 ,改善血流动力学 ,预防心肌肥厚 ,可能与其降低血浆ET 1有关。更多还原

【Abstract】 AIM: To investigate the effects of β 1-adrenergic receptor mRNA antisense oligodeoxynucleotide (β 1-AS-ODN) mediated by the cationic liposomes (DOTAP/DOPE) on the hemodynamics and cardiac hypertrophy of renal hypertensive rats. METHODS: The two-kidney and one-clip (2K1C) rat models were established and divided into five groups: the sham-operated group, the 2K1C group, the 2K1C+inverted ODN (IN-ODN) group, the 2K1C+ antisense oligodeoxynucleotide (AS-ODN) group and the 2K1C+carvedilol group. Single intravenous injection of ODN 0.5 mg·kg -1 was given after four weeks of operation and carvedilol 10 mg·kg -1·d -1 was administrated for 4 weeks. Blood pressure was measured regularly. Hemodynamic parameters, left ventricular weight index(LVWI)and plasma endothelin-1(ET-1) concentration were measured after eight weeks of operation The linear correlation between LVWI and ET-1 were analyzed. RESULTS: Compared with the IN-ODN group, β 1-AS-ODN significantly decreased SBP (P< 0.01), increased ±dp/dt max (P< 0.01), and had an obvious suppressive effect on LVSP(P< 0.05), LVEDP(P< 0.01), LVWI (P< 0.05) and ET-1(P< 0.01). No significant difference was found between the AS-ODN group and the carvedilol group. In addition, LVWI positively correlated with ET-1 (r= 0.749, P< 0.01). CONCLUSION: β 1-AS-ODN mediated by the cationic liposomes has an effective long-term antihypertensive effect with single intravenous injection. It can also improve the hemodynamics and attenuate cardiac hypertrophy. These effects may relate to their effect of decreasing the concentration of plasma ET-1.更多还原