Effect Of Donor JNK Signal Transduction Inhibition On Renal Immunogenicity And Transplant Outcome In Brain Dead Rats

PARTâ… Establishment of a stable brain death model in the ratObjective The brain death model in the rat is widely used,especially in the study of organ transplantation.But this model is unreliable sometimes because of unstable mean arterial blood pressure and cardiac arrest that lead to serious errors of the experiment results.To change this situation, we have established a reproduceable model of gradual onset brain death in rats.Methods Forty adult male 200-250gWistar rats were used for experiment. Brain death was induced by graded inflation of a 3F Fogarty catheter placed intracranially under EEG and blood pressure monitoring,apnea and irresponsive cornea were observed as well.The rats were mechanically ventilated for 6 hr before removal of their kidneys.Complications and mortality are discussed.Results The majority(75%) of the 40 experimental animals could be used as organ donors.After a transient period of autonomic storm,the mean arterial blood pressure remained consistently between 80-100 mmHg,not appreciably different from controls.Conclusion We established a model of gradual onset brain death in the rat, in which the MAP could be sustained normal for at least 6hours.The major complications were unstable MAP and cardiac arrest.Accordingly,this model is reliable and suitable for transplant related studies involving organs from donors with irreversible central injury.PARTâ…¡Kidney transplantation in the rat:a modified techniqueObjective Kidney transplantation model in the rat is important in the research of organ transplantation and kidney diseases.At present,many types of this model were established with some shortcomings in operation time and survival rate.To establish an easy and safe model,a technical innovation on rat kidney transplantation was described in this article. Methods Sixty Wistar rats were selected as donors,and 60 SD rats were used as recipients.The left kidney graft was transplanted heterotopically into the left infrarenal position.Donor abdominal aorta and left renal vein were end-to-side anastomosesed to the recipient abdominal aorta and inferior vena cava,respectively.A novel technique was employed for ureter implantation in our model.Recipient both own kidneys were removed before closing the wound.The operation time and survival rate were observed.Results It took 100-140 minutes to complete the whole surgical procedure. The warm ischemia time was about 8-10 seconds,while the cold ischemia time was 40-60 minutes.Successful rate of the kidney transplantation was 85%.Reasons of operation failure were analysed as the following:stenosis of the anastomotic stoma and thrombosis(6.67%),hemorrhage of the anastomotic(5%),infection(1.67%),unknown reason(1.67%).Conclusion With modifications in the kidney tramsplatation model,the operation time was shortened,especially the time of warm ischemia of the graft and urinary tract reconstruction.Complications of vascular anastomoses and urinary tract reconstruction were parum.PARTâ…¢Effect of donor JNK signal transduction inhibition on renal immunogenicity and transplant outcome in brain dead ratObjective To reduce the renal immunogenicity and improve transplant outcome,we observed the influence of JNK signal transduction inhibition pretreatment on ischemia-reperfusion injury and immunity activation in a rat brain death model.Methods A standardized rat model of brain death was used.Donors were treated immediately after induction of brain death with JNK signal transduction inhibition.Kidney grafts from experimental group and control groups were examined serially up to 7 days by morphology, immmunohistology,and real-time PCR. Results After inhibiting the JNK signal transduction,the intensity of ischemia-reperfusion injury and of acute rejection was reduced.Cellular infiltration,transcription of mRNA of some representative proinflammatory mediators and MHC-â…¡molecules in the grafts were diminished.Rats with kidneys from brain-dead donors that had received such pretreatment survived significantly longer than those from untreated brain-dead donors.Conclusion The JNK signal transduction inhibition pretreatment in brain dead rats can improve kidney quality,reduce the renal immunogenicity and improve the graft survival.