The Protective Effects Of Tacrolimus On The Expression Of Heat Shock Protein In Rat Kidneys With Ischemia/reperfusion Injury Stress

Objective: Ischemia-reperfusion injury is on inevitable process in renal transplantation. The mechanism is very complex and presently there is no effective medicine or therapy. Tacrolimus is an immunosuppressive drug used for the prevention of acute organ graft rejection. Some studies have demonstrated that Tacrolimus can inhibit glycosylation of cell adhesion molecules which are involved in ischemia-reperfusion injury. In this experiment,we investigated the protective effects of Tacrolimus on the expression of heat shock protein in rat kidneys with ischemia/reperfusion injury.Methods: The ischemia-reperfusion injury model in rat was established with its right kidney excised and left renal artery blocked for 45 minutes. In this study ,117 SD rats were randomly divided into sham operation group (split the renal artery, without blocking the renal art) ,control group (block the renal artery and inject placebo water),and experiment group(block the renal artery for 45 minutes and inject Tacrolimus 5-10 minutes before the operation). The left kidney samples were collected at 15- minute, 30- minute, 1- hour, 2 -hour, 6-hour, 12-hour, 1- day, 3 -day and 7- day ischemia-reperfusion time respectively.The flow recovery time was recorded the renal function was compared with that before operation,and the expression of heat shock protein and its pathological changes in the 3 groups were compared by using immunohistochemistry.Results: (1) Blood flow recovery time in the control group was much longer than that in the experiment group (186 ±54s vs. 72±31s p<0.01); (2) The rats in the control group did not recover well (weight-gaining) (1st-9.15% 3rd -9.06%, 7th-7.56%), but those in the experiment group recovered well (1st-10.12%, 3rd+1.27%, 7th+3.94%). (3) In the control group creatine level increased at 6th hour and reached the peak at 12th hour. After the 1stdayreperfusion, creatine declined, and at 3rd day it went back to the normal level. In the experiment group creatine level increased at 6th hour, kept this level, and recovered at 3rd day (creatinine level at 12 hour in the sham operation group vs the experiment group:78.2 μmol/L vs. 50.0μmol/L,P<0.05). (4) The pathological progress in the control and experiment groups was alike, started at 2nd hour and become obvious at 12th-24th hour after reperfusion. The pathological change was weaker in the control group. At 12th hour afer operation,the regeneration of tubule cell was observed,and at 7th day more tubule regeneration and less fibroplastic proliferation was observed in the experiment group. (5) The expression of heat-shock protein 72 in the control and experiment groups was similar: started at 1 hour, peaked at 6th hour, and drawed off after 12 hours. The expression was more intensive in the control group than that in the experiment group(176.06±28.91 vs. 140.94±22.11 p<0.01)Conclusions: In the experiment group, the SD rat recovered rapidly; creatine level was low, and the injury pathological change ameliorated. Tacrolimus can attenuate ischemia-reperfusion injury in the kidney.