Expression of human atrial natriuretic peptide gene and the effective for the blood pressure and the histomorphology of the kidney in the spontaneously hypertensive rats
Expression of human atrial natriuretic peptide gene and the effective for the blood pressure and the histomorphology of the kidney in the spontaneously hypertensive rats
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发表时间：
2014
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通讯作者：
Sun Hu
中科院分区：
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作者：
Sun Hu
目的：探讨人心房钠尿肽（hANP）基因转染对自发性高血压大鼠（SHR）血压及肾脏组织形态学的影响及长期疗效。方法：将12只8周龄雄性SHR随机分为两组。感染组（n=6）注射pcDNA3.1-CMV-h ANP质粒。对照组（n=6）在同一部位注射pcDNA3.1-CMV质粒。基因转染后，通过尾动脉测量和放射免疫技术，每周测定SHR的收缩压和血浆h ANP水平。10周后处死动物，采用RT-PCR和Western blot检测h ANP基因表达情况，HE染色和Masson染色观察肾脏组织形态学变化。结果：pcDNA3.1-CMV-h ANP质粒注射SHR后第1周，感染组血压开始下降，与对照组比较，血压差异显著（12.0 ± 3.1mmHg，P0.05），持续10周，放射免疫法检测到感染组h ANP水平升高。逆转录聚合酶链反应（RT-PCR）和Western blot结果表明，hANP基因在肌肉中能有效表达，而对照组无表达。组织形态学分析显示感染组肾组织损伤减轻。结论：通过肌肉注射的方法将hANP基因导入SHR，可在SHR肌肉中有效表达，表达蛋白可释放到血液循环中。hANP基因不仅能稳定降压，而且能预防高血压靶器官肾脏的损伤，提示hANP基因治疗人类高血压的可行性。
Objective:To investigation the expression,the long term and the effective for the blood pressure and the histomorphology of the kidney in the spontaneously hypertensive rats(SHR)after the human atrial natriuretic peptide(h ANP)gene delivery. Methods:Twelve eight-week-old male SHR were divided into two groups randomly. The skeletal muscle of the SHR in infected group(n=6)were injection of pc DNA3.1-CMV-h ANP plasmid. Control group(n=6)were injection of pc DNA3.1-CMV plasmid into the same locus. After the gene delivery,the systolic pressure and the level of h ANP in the plasm of the SHR were both measured every week by measuring the caudal artery and utilization of radio-immunity technique. After ten weeks the Animals were put to death,the station of the expression of h ANP gene were measured by utilizating RT-PCR and Western blot;the effective of histomorphology of the Kidney were evaluated by Hematoxylin-Eosin(HE)and Masson. Results:From the first week after the injection of pc DNA3.1-CMV-h ANP plasmid into SHR,the blood pressure of the infected group began to reduce compared with the control group.A significant blood pressure difference(up to 12.0+3.1mm Hg,P0.05)continued for 10 weeks.The high level of h ANP in the infected group was detected by the Method of radio-immunity. The result of reverse ranscriptionpolymerase chain reaction(RT-PCR)and Western blot showed that h ANP gene can be expressed efficiently in the muscles,but the control group had no expresstion. Tissue morphology analysis shows that renal injury were attenuated in the infected group. Conclusion:h ANP gene were delivered into SHR through muscle injections,it can be expressed efficiently in the muscles and its expresstion protein can be released into blood circulation in SHR. it can not only stably deduce blood pressure,but also prevent the injury of the renal of target organ of hypertension.That result suggests the feasibility of h ANP gene therapy in human hypertension.