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Effect Of Ultrasound Mediated Liposome Microbubble On Biological Behaviour Of Rat Vascular Smooth Muscle Cells

Posted on:2006-08-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:P ZhangFull Text:PDF
GTID:1104360185970452Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background and objective: Neointimal hyperplasia is the major pathogenesis of restenosis(RS), wich results from phenotypic modulation, proliferation, migration, inadequate apoptosis of vascular smooth muscle cells(VSMCs) and extracellular matrix deposition triggered by vascular injury. A vast array of therapies, including oral antiplalete agents, anticoagulate agents, statins, antiproliferative agents, intracoronary bracthytherapy, gene therapy and drug-eluting stent, have reduced incidence of RS, but not eliminated the problem. Therefore, efforts to overcome the challenge of neointimal hyperplasia are still actively pursued. Recently, the rapid progress of echo-contrast agents that recirculate throughout the blood volume and the deveopment of targeted agents open new possibilities for therapy with microbubbles. Ultrasound alone has been shown to cause bioeffects of irradiated tissues and cells, such as inhibiting cell proliferation, migration and adhesion, as well as inducing apoptosis. Cavitation is associated with these effects. Furthermore, effects of microbubbles when combined with ultrasound were also investigated. As artificial cavitation nuclei, microbubbles not only lower the threshold of cavatation, reduce the amount of energy needed to cause cavitation from ultrasound, and increase the ultrasound-induced bioeffects, but also can be cavitated with ultrasound energy for site-specific local delivery of drug, gene and protein. So, if the targeted carrier role of microbubbles and the cavitation effect of ultrasound can be combined effectively, a novel potential therapeutic paradigm will be developed for preventing RS and have great promise for clinical applications. This research is designed to prepare a kind of paclitaxel loaded liposome microbubbles and investigate its effect on proliferation, migration, apoptosis and phenotypic modulation of rat VSMCs, with the exposure of ultrasound in vitro, and make an approach to the mechanism.Methods:1. Primary VSMCs isolated from the thoracic aortae of SD rats were cultured by plant...
Keywords/Search Tags:Vascular smooth muscle cells, Paclitaxel, Proliferation, Migration, Apoptosis, Phenotypic modulation, Ultrasound, Calcium, Liposome microbbubles, Cavitation, Cell cycle, Cytoskeleton
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