| Renal transplantation, most of which is cadaver renal allotransplantation at present limited by all kinds of techniques and environment, is a very effective therapy for end stage renal disease(ESRD). In recent years, with the development of matching technique, immunosuppressive agents and surgical technique, the incidence of acute rejection episodes has decreased significantly, short-term survival rates of recipients have increased evidently, and 1-year survival rates of recipients has arrived to 90% or more than 90%. While there has no significant increase for the half life and long-term survival rate of graft. Chronic renal allograft dysfunction (CRAD), which is mainly caused by chronic allograft nephropathy (CAN), has become a main cause to reduce the long-term survival of graft. The allograft in patient with CAN occurs progressive irreversibilit hypofunction. The wide angiopathy, interstitial fibrosis, glomerulosclerosis and renal tubular atrophy can be seen pathologically, and progressive proteinuria, hypertension and increase of serum creatinine can be found clinically. CAN can be caused by immunologic factors and non-immunologic factors. Now people is paying more and more careful attention to non-immunologic factors concluding donor-related factors, contribution-related events, post-transplant environment and immunosuppressive agents used to prevent acute rejection, et al.Cellular signal transduction system is a intracellular transducting process for environmental signals. This system is made of a series of proteins. Mitogen-activated protein kinases (MAPK), which is an important point in cellular acting protein network, takes part in process for exocytic signal from surface of cell to inner of cell and is considered as co-via of intracellular signal transduction. At present the Ras-MAPK pathway, namely Ras-ERK(extracellular signal-regulated kinase) pathway, mainly takes part in many cytokines guided cell proliferation .The stimulation of many kinds of extracellular mitoses is related with ERK activation. The protein-tyrosine- phosphatase receptor, G-protein coupling receptor and cytokine receptor can activate ERK cascade, among which Ras can regulate cellular growth and differentiation as signal on-of molecule. The activation of ERKis related with proliferation of mesangial cell in kidney fibrosis. A large amout of studies have also shown that MAPK makes an important action in the occurrence and development of many kidney diseases, specially Ras-ERK making action in glomerulosclerosis and fibrosis of renal parenchyma caused by many kidney diseases.CAN represent cumulative and incremental damage to nephrons from time-immunologic and nonimmunologic causes. The pathology of CAN is extremely complex, and mang factors including all kinds of grow factors, adherent molecules and cytokines, especially TGF-pl (transforming growth factor betal) and Angll (angiotensin II) are involved. The date indicate that ERK pathways can be activated by Angll via TGF-pland TGF-pl plays a main role in TGF-pl-induced fibrosis of renal parenchyma. The functional and morphologic findings are well characterized, but at present there is no complete clarification on mechanism of CAN, and there are few therapeutic methods for CAN and their therapeutic effectiveness is poor. The regulating mechanism of corresponding cells and interstitial fibrosis with CAN is complicated, too. No systemic reports about the action of MAPK cascade in CAN have been seen. Now the advanced clarification of MAPK cascade physiologically can provide direction and support for the researches of signal transduction in development of CAN oObjects:1 > To explore the expression of Ras and ERK signal transduction molecules in normal kidney, kidney with ischemia-reperfusion and allograft with CAN, so as to make clear the role of Ras-ERK signal transduction pathway in CAN.2> To study the changes of patient's conditions and expression of Ras, ERK in renal allograft after the patients with CAN have received the comprehesive therapy with immunosuppressive agents a... |
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