Lu Ping, Yuan Lifen, Wang Yuqiang, Du Qin, Sheng Jing
Department of Geriatrics, Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.
Int J Clin Exp Pathol. 2012;5(7):698-706. Epub 2012 Sep 5.
To investigate the effects of RNA interference targeting AGT on early atherosclerotic lesion in the hypertensive state.
Hypertension and atherosclerosis rats were treated with GPE nanoparticles carrying AGT shRNA. Systolic blood pressure and heart rate were measured for 2 consecutive weeks. Three days after treatment, the mRNA and protein expressions of AGT in the liver were measured by PCR and western blot assay, respectively. The blood levels of AGT and Ang II were determined by ELISA. H&E staining and electron microscopy were performed.
Three days after AGT shRNA treatment, the mRNA and protein expressions of AGT in the liver were markedly reduced and the blood levels of AGT and Ang II dramatically decreased as compared to the remaining 3 groups (P < 0.05). Three days after AGT shRNA treatment, the blood pressure was reduced by 27 ± 4 mmHg when compared with that at baseline (P < 0.05). About 11 days after AGT shRNA treatment, the blood pressure began to increase. The blood pressure remained unchanged in the remaining 3 groups. Microscopy showed the atherosclerotic lesions were markedly attenuated in AGT shRNA treated rats but the liver and kidney functions remained stable (P > 0.05) when compared with the remaining 3 groups.
Transfection with GPE nanoparticle carrying AGT shRNA can stably lower the blood pressure and improve the atherosclerotic lesions which lead to the delayed development of early atherosclerotic lesions in hypertension rats with concomitant atherosclerosis.
研究靶向血管紧张素原（AGT）的RNA干扰对高血压状态下早期动脉粥样硬化病变的影响。
用携带AGT小干扰RNA（shRNA）的GPE纳米颗粒处理高血压和动脉粥样硬化大鼠。连续2周测量收缩压和心率。治疗3天后，分别通过聚合酶链反应（PCR）和蛋白质免疫印迹法检测肝脏中AGT的信使核糖核酸（mRNA）和蛋白表达。采用酶联免疫吸附测定法（ELISA）测定血液中AGT和血管紧张素II（Ang II）的水平。进行苏木精-伊红（H&E）染色和电子显微镜检查。
与其他3组相比，AGT shRNA处理3天后，肝脏中AGT的mRNA和蛋白表达显著降低，血液中AGT和Ang II水平显著下降（P<0.05）。AGT shRNA处理3天后，与基线相比血压降低了27±4毫米汞柱（P<0.05）。AGT shRNA处理约11天后，血压开始升高。其他3组血压保持不变。显微镜检查显示，与其他3组相比，AGT shRNA处理的大鼠动脉粥样硬化病变明显减轻，但肝脏和肾脏功能保持稳定（P>0.05）。
用携带AGT shRNA的GPE纳米颗粒转染可稳定降低血压并改善动脉粥样硬化病变，从而延缓伴有动脉粥样硬化的高血压大鼠早期动脉粥样硬化病变的发展。
