| AAA is a kind of limited dilatation disease. With the development of aging and the changes of diet structure, the episode of AAA increases gradually. In tradition, it is considered that AAA is induced by infection, wound and atherosclerosis and facilitated by hypertension, smoking and so on. Nevertheless, recently it is thought that multiple factors responsible for this desease, including genetic, environment and biochemistry. The most risk of the desease lies in the death opportunity due to aneurysm growth and disruption. Through aortic reconstruction and endovascular repair can cure big aneurysms, we prefer to operation treatment for small aneurysms because of the high risk and limits of the operation. The pathogenesis of the earlier AAA is still unknown, which has a direct impact on the prevention and cure effect. With the development of gene techniques, it can play an important role in the aneurysm therapy. Some data showed that macrophages can facilitate the development the AAA by produting MMPs. MCP -1 gene can not only attract the rolling of monocyte macrophages, but also regulate the expression of adhesive molecular ( VCAM and ICAM ) , playing an important role during the processes of monocyte migration into the arteric wall. Antisense technology of gene therapy can inhibitate the disorder expression of lethal gene and has a good application. Microparticles as a new gene transfer carrier,can easily enter the tissue, then remain there, release slowly, which showed light future in the study of gene therapy. In this paper, we will discuss the role of MCP - 1 gene on the earlier AAA at first. Then we will evaluate the reliability and effectivenese of microparticle carrier by constructing microparticle carriered LNCX - anti -MCP -1 gene transfer system and observing the gene transfer effect.MethodsFistly we will studu the basic mechanism of AAA. Rat AAA model was made by perfusion PPE elastase through the abdominal aorta,and the specimen was obtained on postoperativeday 3,7,14,28,respectively. Specific elastic fiber staining was used to observe the disruption of elastic fiber in aortic wall. Immu-nohistochemistry staining of CD68 was applied to observe the microphage infiltration. The in tisu hybridization and western blot of MCP - 1 and MMP - 2 were used to study the expression of mRNA and protein. Thus we can analyze the facilitated function of MCP - 1 gene to the microphage adherence and infiltration on the earlier AAA. Establish microparticle mediated antisense MCP - 1 gene transfer system,by molecular cloning technique. LNCX carrier was digested by Hpa I and Cla I enzyme, and pBS - SK + MCP - 1 plasmid was digested by Sma I and Cla I enzyme, then fragments were recovered. The same end was connected by T4 DNA banding enzyme, thus MCP - 1 gene was inserted into the LNCX multiple clone site on opposite direction. Under the regulation of intra - promo-tor , anti sense MCP - 1 mRNA sequence was producted. After applification extraction and evalution, ultrasound emulsification was used to establish microparticle gene transfer system carrying MCP -1 DNA. Then the physical character was observed. At last in vivo transfection microparticle mediated antisense MCP - 1 gene was applied to study the inhibition of MCP -1 gene to the development of AAA. After rat AAA model was made, rats were devided into microparticle -DNA group and 2 control groups. Localization transfetion to the abdominal aorta was performed, and the changes of abdominal aorta diameter was observed after 2 week. Polymerase chain reaction (PCR) was used to estimate the reliability of microparticle as gene transfer carrier,and in tisu hybridization and western blot were applied to observe the inhibition to the endogenous MCP -1 gene expression after antisense gene transfection.ResultsAt present, many pathogenesis about AAA were obtained from mature AAA specimen,so we can't know the information about the initial AAA. Compared with clinical study,animal model showed apparent superiority on the pathogenesis research of earlier AAA. The...
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