| Allogenic kidney transplantation has become an efficient treatment of end-stage renal disease. Since the improvement of tissue matching and immune inhibitor, the renal short-term survival rate has been greatly increased to as high as 95% one year after operation. However, its long-term survival rate, which is only 50% ten years after operation, hasn't been greatly increased yet. Chronic allograft nephropathy (CAN), the main cause of planted renal function failure, influences renal long-term survival rate and is a big problem to be urgently solved in clinic. Nowadays it has been widely accepted that CAN is due to many factors including self-antigen dependence and non-self-antigen dependence and is closely related to immune factors(rejection) and non-immune factors(ischemia period), but the mechanism is unclear. The prevention of renal injuries due to cold and hot ischemia and protection of the transplanted kidney from rejection will be of great significance in reducing the episode of CAN and increasing renal long-term survival rate.Previous studies have shown that repeated transient ischemia in advance could stimulate planted organs to tolerate longer subsequent ischemia injury. This kind of special phenomenon is called ischemia preconditioning(IP). Using some drugs to simulate or affect the procedures of IP on purpose in order to protect kidney as IP does is called pharmacologic preconditioning(PP). Up till now, many researches of IP have been conducted on heart to alleviate ischemia injury of heart. It can be predicted that renal ischemia injury and its degree are closely related to renal tolerance to ischemia. IP can prevent acute rejection and then reduce the episode of CAN by means of relieving ischemia reperfusion injury and antigen exposure. Some preliminary studies also showed that IP could occur in kidney and could alleviate renal damage in aspects of renal function, energy metabolism and histology, but the mechanism remains unclear. Some researches with coronary artery endothelial cells or aortic endothelial cells revealed that IP could decrease the expression of ICAM-1. In liver, IP could prevent up-regulation of the expression of P-selectin, while in heart, IP could reduce the expression of TNF-α. However, there have been few studies of planted renal IP and its influence on adhesion molecule and cytokin.In our study, we expect to confirm that IP can alleviate both ischemia reperfusioninjury and rejection by down-regulating expression of MHC-II molecule to prove that IP can lower the incidence rate of CAN by the alleviation of renal ischemia-reperfusion injury and decrease in incidence of transplanted kidney rejection. For the purpose of convenient application of the experimental results in clinical practice, we used some drugs to simulate IP. The main contents of the experiment are as follows:1. Influence of IP and PP(Ligustrazine,cAMP and Zenepax) in cultured human glomerular endothelial cells on the expression of adhesion molecule and MHC-II molecule;2. In vivo changes of the expressions of adhesion molecule, MHC-II molecule, IL-2, TNF-α in serum and infiltration of leucocytes after IP and PP in order to discuss the mechanism of preconditioning relieving renal ischemia reperfusion injury and changes of immunogenicity;3. To set up rat allogenic kidney transplantation model in order to confirm that IP and PP can alleviate reperfusion injury and rejection and protect planted renal function.Main results:1. Influence of preconditioning on expression of adhesion molecule in cultured human glomerular endothelial cells: Expressions of ICAM-1, P-Selectin, E-Selectin and MHC-II in glomerular endothelial cells increased greatly following A/R but decreased greatly after IP and PP.2. In vivo renal ischemia reperfusion injury could lead to the increased expressions of ICAM-1, P-Selectin, E-Selectin and MHC-II in glomerular endothelial cells, renal tubule epithelial cells and interstitial adhesion molecules, increased concentration of TNF-α, IL-2 and creatinine in serum and great...
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