| In kidney transplants, the initial unavoidableischemia/reperfusion injury occuring secondary to organ retrieval,storage, and engraftment has a profound influence on eventsfollowing renal transplantation. Severe ischemia/reperfusion injuryof graft will result in transplant acute tubular necrosis (ATN). Such acondition is clinically vexing, producing diffculties for the patientand physician alike. These include uncertainty in assessing thecoincident presence of acute immunological rejection, whichnecessitates increased use of diagnostic tests both invasive andnoninvasive, prolonged hospitalization, higher costs, and delayedrehabilitation potential. In addition, continuing dialysis aftertransplantation may produce its own set of problem. It is notunreasonable to accept the hypothesis that ischemia/reperfusioninjury provokes acute immunologocal rejection according to manyclinical studies that showed the prevalence of acute rejection onpatients of ATN is higher than that on patients who had early renalfunction. The early injury had been associated with late renalallograft deterioration and had been considered as a main antigen-independent risk factor. Therefore, it is an important clinicalproblem in solid organ transplantation that how to reduceischemia/reperfusion injury of transtlanted kidney. In past, all kinds- 5 -$=$BX* 4xmK Mt$&&xof drugs were used to prevent ischemia/reperfusion injury; however,the problem with this approach is that such interventions areprimarily directed against just one aspect of complicated andvariable pathogenesis of reperfusion injury, these treatments provide,at best, incomplete protection. Up to now, a treatment which hascomprehensive biochemical effects is not found to cope with theischemia/reperfusion injury of transplanted kidney, but it is known tdall that the most potent protective maneuver in the history of medicaltreatment is hypothermia. So we first put forward a new view that therecipient is made mild hypothermia before transplant operation, andafter opening the blood of recipient the transplanted kidney gets themild hypothermic reperfusion which will mitigate theischemia/reperfusion injury of transplant.OBJECTIVEl. To found an animal model of renal cold ischemia/reperfusioninjury by perfusion in situ in rats, which is more suitable toclinical setting.2. To demonstrate the effect of early ischemia/reperfusion injury onlate renal function.3. To further illustrate the related mechanism betweenischemia/reperfusion injury and acute rejection from T cellcostimulatory molecules B7.4. To clarify the protective effects of mild hypothermia duringreperfusion on renaI ischemia/reperfusion injury on abovementioned model and ilIustrate the mechanism of the protection.MATERIALS AND METHODSAn animal model of renal cbld ischemia/reperfusion injury- 6 -was established according to Takada's measure, which was modifiedby us. Three groups were studied: Group A: these animals whichunderwent cold ischemia/reperfusion were subjected tonormothermic reperfusion. Group B: these animaIs which underwentcold ischemia/reperfusion were made mild hypothermia(32 -- 33oC)during reperfusion and maintained fOr 60 min. Group C: controlrats: these animals were subjected to a right nephrectomy withoutclaming of the vessels of the left kidney. The dynamic changes ofserum creatinine and BUN after reperfusion and the renal tissuepathological and proximal tubule cell ultrastructural analysis atreperfusion 24 hours were studied. Protein excretion was monitoredfor up to 24 weeks in animals underwent cold ischemia/reperfusion...inJury. Yhe level of plasma malondialdehyde (MDA) and superoxidedismutase (SOD) was detected, The renal tissue was homogenized toevaluate the activities of Na+. K+ -- ATPase, Ca2+ -- ATPase and PLA,by spectrophotometry. Total RNA was isolated from the renal tissuesusing Trizol reagent. Message R... |
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