Dissertation > Medicine, health > Surgery > Urology ( urinary and reproductive system diseases) > Kidney disease

Construction of Recombinant Adenovirus Carrying Human HO-1 Gene and Its Protection Against Renal Ischemia/Reperfusion Injury in Rats

Author LvJinXing
Tutor YanChunYin
School Suzhou University
Course Department of Urology
Keywords Recombinant adenovirus Gene therapy Cytoprotective Human heme oxygenase -1 ( hHO - 1 ) Ischemia - reperfusion injury ( IRI )
CLC R692
Type PhD thesis
Year 2005
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Ischemia-reperfusion injury and acute rejection are the two most important factors affecting graft function. For vascularized organ transplantation, always varying degrees of ischemia-reperfusion injury. Severe delayed graft function recovery can occur even primary function. Although most of ischemia-reperfusion injury is recoverable, but its impact can not be ignored, and often result in prolonged hospitalization, increase the difficulty of the use of immunosuppressive agents, to extend the duration of dialysis, the additional cost. In addition, ischemia-reperfusion injury can cause increased immunogenicity of the graft, precipitating acute and chronic rejection. More and more evidence that: is closely related to long-term loss of renal function and ischemia-reperfusion injury. So the impact is almost extreme due to the ability of the the traditional systemic immunosuppressive agents in the control of acute rejection, graft survival in non-antigen-specific factors have received increasing attention. In recent years, transgenic technology having cytoprotective and / or immunosuppressive effects gene by in vitro transfection of graft gradually become a very promising strategy to reduce the damage of the graft. Heme oxygenase -1 (HO-1) is the rate-limiting enzyme in heme catabolism of heme can be degraded to carbon monoxide (CO), ferrous ions (Fe 2 ) and biliverdin The hormone, which is rapidly degraded to bilirubin. HO-1 expression was induced isozyme HO isozyme only. HO-1, also known as HSP32 is a heat shock protein (heat shock protein HSP) family. And other HSP induction of HO-1 expression is one of the most important protection mechanisms in the cell stress. HO-1 expression in the physiological state less (except spleen), but a variety of stress factors (such as: inflammation, ischemia, hyperoxia, hypoxia, or radiation, etc.) so that it was significantly increased. More and more evidence that:, HO-1 overexpression by cytoprotective and immunomodulatory mechanism to protect an organ or tissue from the inflammatory and immune-mediated injury in organ transplantation. Although a variety of factors that can induce over-expression of HO-1, such as heme, cobalt porphyrin, but transgenic technology (cold vitro transfection) is considered to be most tissue-specific and the most attractive way. The adenovirus vector system having a safe and effective, and do not integrate with the host chromosomal DNA, the capacity to carry the exogenous gene, easy preparation and purification, a vector system is currently widely used in the field of gene therapy. In addition, the adenovirus has a wide range of host cells, it can infect dividing cells, can also infect non-dividing terminally differentiated cells, which in vivo transfection renal cell gene therapy to provide a strong guarantee. Traditional gene therapy there are many defects, such as the target gene targeting poor short-term and expression. Renal transplantation, there are sufficient conditions for the donor kidney accurate transfection. In addition, although the transgenic immune

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