| Hypertensive disease is a major disease which affects many people in the world. Hypertensive individuals are more likely to develop other cardio-vasvasocular disorders such as peripheral vascular disease, coronary heartdisease, congestive heart failure and cerebrovascular diseases. Essential hypertension appears to be a polygenic disease with significant environmental and dictary components. Abnormality of the atrial natriuretic polypeptide has long been documented in the pathogenesis of hypertension. Because of the short-time Action, lots of ill effect and the worse compliance, traditional drug treatment can not control hypertensive disease which need long time drug treatment. With the development of molecul heart angio pathilogy, gene therapy has become a new pathway of hypertensive disease and has better prospect. In the last ten years, gene therapy has a conspicuous achievement, but most of them still has been a transition from animal experiment to clinical application. It has a long distance from the target of clinical application. The chief problem is (1) settling the target gene, which is the premise of the gene therapy; (2) constructing carrier, constructing the safety, effective, micro-immunogenicity carrier is hot spot of gene therapy. (3) gene therapy Technique, which is the key point of the gene therapy. Alough primary hypertension involve in lots of genes and lots of predisposing genes still not being known, the Regulation of some blood vessel activity substance has been cleared-cut, and achieved a outstanding progress in hypertension animal model. Many clinical investigations and Animal experiments has confirmed that ANP played a important role in the episode procedure of hypertension. It is certified that the blood pressure of hypertension animal and the patien was descented by vein dribbling. The blood pressure of mice of transmitting ANP gene can be descented for a long time, but absenting the gene lead to step-up. On the background, it is reported that by transgening ANP of animal or Homosapiens to the hypertension animal,it has achieved satisfactory effect. It is made clear that transgene Method can be used in therapy of hypertension, ANP gene could be one of the good selective gene. However, because of gene carrier not being finished, the objective of long-term, utility, safety, Stable has been not realized. Recently, scientis are very interested in gene therapy which plasmid is adopted to be carrier. Becourse the plasmid has a lot of advantages, such as easy to be established, no infectivity, not inducing carcinoma, micro-immunogenicity, long expression time, no serious ill effect, not integration with gene of host cell, These are good at the application and extension in gene therapy. To explore the potential theraputic effects of atrial natriureticpeptide gene delivery, and to gain the perspective of long term and stable expression of human atrial natriuretic peptide, we delivered human atrial natriuretic peptide cDNA in pcDNA3.1-CMV-plasmid. we produced the enough recombination plasmid. Muscle Injection of pcDNA3.1-CMV-ANP plasmid into the adult spontaneous hypertensive rats was performed.expression of human atrial natriuretic peptide in rats was assessed by the Method of radio-immunity and reverse transcription polymerase chain reaction (RT-PCR). Blood pressure and urinary excretion of microalbumin was monitored. Morphologial analysis was used to evaluated the renal injury and the cardiovascular remodeling. After the injection of pcDNA3.1-CMV-ANP plasmid into SHR, a maximal blood pressure reduction of 15mmHg was observed beginning within three weeks, as compared with control rats receiving hANP containing the lacZ reporter gene. A significant blood pressure Difference (up to 12.0+2.55mmHg, p<0.05, n=6, ANOVA) continued for 10 weeks. A long term expression of human atrial natriuretic peptide was detected by the Method of radio-immunity. The result of reverse transcription-polymerase chain reaction (RT-PCR) showed that... |
