The Immunosuppressive Effects And Mechanisms Of Ginsenoside Rd On Immunological Reiection In Rat Allograft Renal Transplantation

Aims:Immunosuppressive agents such as cyclosporine A (CsA), azathioprine, prednisone, are commonly used in clinical cure, but the low specificity and high side effects restrict theirs application. Ginsenoside Rd, as a compound of pseudo-ginseng, has many pharmacological effects in immune system. In this study, the immunosuppressive mechanisms of ginsenoside Rd were investigated in rat allograft renal transplantation.Methods:(1)The model of rat allograft renal transplantation was established from SD rat to Wistar rat. The methods of end-to-side vascular anastomosis and ureter implantation were used.(2)The rats were divided into6groups, namely normal group (saline, im.), model group (55%propylene glycol, im.), positive control group (CsA,5mg/kg, im.), ginsenoside Rd low, medium and high dose groups(10,20and40mg/kg, im.). Drug treatment started one day before renal transplantation operation, once per day for two weeks. On the3,5and7day after operation, changes of histopatholgy in renal tissue was estimated, and the degree of.acute rejection was evaluated. The activitations of NF-κB and NFAT signal pathways and the expression of caspase-3in cytoplasm of rat renal tissue were detected by Western blot analysis. Besides, the survival time of rats after operation was recorded.Results:(1) The model of rat allograft renal transplantation was stable with the success rate of70%. The "hot" ischemia time of renal allograft was less than1s; the "cold" ischemia time was about60±10min; renal artery anastomosis time was40±5min; renal vein anastomosis time was20±5min; and the whole operation time was2.6±0.5h.(2) The survival time of rats was8.67±1.15d in model group and32±4.58d in positive control group, and was16±4.58,16.67±4.72and15.33±3.51d in ginsenoside Rd low, medium and high dose groups, respectively.(3) The changes of histopatholgy in renal tissue:acute rejection in model group was gradually aggravated on the3,5and7day after renal transplantation operation, and it was inhibited by CsA and low, medium and high doses of ginsenoside Rd(P<0.01).(4) The activitation of NF-κB signal pathway:compared with normal group, the expressions of NF-κB/p65, IKKβ and p-IκBα were obviously increased in model group (P<0.01), but were decreased in groups treated with CsA and Rd on the7day after operation (P<0.05or0.01).(5) The activitation of NFAT signal pthway: compared with normal group, the expressions of CNA, NFAT1in model group were increased on the3,5and7day after operation (P<0.05or0.01), but were decreased in groups treated with CsA and Rd on the7day after operation, especially in ginsenoside Rd medium and high dose groups (P<0.01).(6) The expression of caspase-3:compared with normal group, the expressions of caspase-3in model group were increased on the3,5and7day after operation (P<0.05,0.01and0.01), but were decreased in groups treated with CsA and Rd, especially on the7day after operation (P<0.05or0.01).Conclusions:(1) In this study, we successfully established the stable and simple model of rat allograft renal transplantation.(2) Ginsenoside Rd could inhibit the acute rejection and prolonged the survival time of rats after renal transplantation operation.(3) Ginsenoside Rd could inhibit the activitations of NF-κB and NFAT signal pathways and the expression of caspase-3.