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目的 :探讨阳离子脂质体混合物 (DOTAP/DOPE)介导的 β1受体反义基因治疗对两肾一夹 (Gold blatt)肾性高血压大鼠血压及血流动力学的影响 ,寻求脂质体与 β1反义寡核苷酸 (β1 AS ODN)混合的最佳转染比例。方法 :用雄性SD大鼠制造两肾一夹 (Goldblatt)肾性高血压模型。β1寡核苷酸 (β1 ODN)末端用FITC标记 ,DOTAP/DOPE与 β1 AS ODN的摩尔比率分别为 0 ,1.5 ,2 .0 ,2 .5 ,3.0 ,经鼠尾静脉注射。监测血压 ,8周后测定血流动力学指标。结果 :FITC标记的 β1 AS ODN主要分布在非钳夹肾动脉一侧的肾近曲小管上皮细胞的细胞浆中。当比率为 2 .0时 ,可使血压下降维持 2 7d ,血压最大下降 39mmHg ,其降压效果及维持时间最好。比率 2 .0组的左心室收缩压、左室舒张末压降低 (P <0 .0 5 ,P <0 .0 1) ,左室最大收缩和舒张速率明显升高 (P <0 .0 1,P<0 .0 1) ,明显地改善了心功能。结论 :以 β1受体为靶基因的反义基因治疗有效 ,阳离子脂质体去掉可以增加静脉注射AS ODN的疗效 ;阳离子脂质体与 β1 AS ODN以不同的比率混合后注射 ,其降压效果及维持时间以及对血流动力学的影响有差异 ,当比率为 2 .0时最好。而且 β1 AS ODN没有中枢神经系统及减慢心率的不良反应。
Objective: To investigate the effect of cationic liposome mixture (DOTAP / DOPE) -mediated β1 receptor antisense gene therapy on blood pressure and hemodynamics in renal hypertensive rats with two bladders (Gold blatt) The optimal ratio of transfection to β1 antisense oligonucleotide (β1 AS ODN) was obtained. Methods: Two-kidney-one kidney (Goldblatt) model of renal hypertension was established in male SD rats. The end of β1 oligonucleotide (β1 ODN) was labeled with FITC. The molar ratio of DOTAP / DOPE to β1 AS ODN was 0, 1.5, 2.0, 2.5, 3.0, respectively. Blood pressure was monitored and hemodynamic parameters were measured after 8 weeks. Results: FITC-labeled β1 AS ODN mainly distributed in the cytoplasm of renal proximal tubule epithelial cells on the side of non-clamp renal artery. When the ratio of 2.0, the blood pressure can be maintained for 2 7d, the maximum blood pressure decreased 39mmHg, the antihypertensive effect and the best time to maintain. The rates of left ventricular systolic pressure and left ventricular end-diastolic pressure (P <0.01, P <0.01) in the ratio of 2.0 were significantly increased (P <0.01) , P <0.01), significantly improved cardiac function. CONCLUSION: Antisense gene therapy with β1 receptor as target gene is effective. Removal of cationic liposomes can increase the therapeutic effect of AS ODN intravenously. Cationic liposomes and β1 AS ODN are mixed and injected at different ratios, and the antihypertensive effect And maintenance of time and hemodynamic effects are different, when the ratio of 2.0 is best. And β1 AS ODN has no central nervous system and heart rate adverse reactions.