The Local Arterial Infusion Of Rabbit-anti-rat Thymocyte Globulin In A Rat Model Of Limb Allotransplantation: An Experimental Research

Objective:In order to investigate the impact of different ways of administration ofrabbit-anti-rat thymocyte globulin (rATG) on the systemic state of recipient and thesurvival of allograft in a rat hind limb allotransplantation model. Find a new method oftreatment which has less impact on the general state and better immunosuppressiveeffect.Method: In situ autologous limb transplantation was conducted in6inbred Lewis (LEW,RT11) rats, which were regarded as the autotransplantation control group (group A).Then limb allptransplantation models were built using inbred Lewis rats (n=24) as therecipient and inbred Brown Norway (BN, RT1n)(n=12) as the donor. They wererandomly divided into4groups according to the different administration method ofrATG, including the allotransplantation control group (group B, no treatment after thetransplantation, n=6), the intraperitoneal injection group (group C, intraperitonealinjection of rATG,1mg/kg/d, q.d., n=6), the intravenous infusion group (group D,sustained infusion of rATG through femoral vein,1mg/kg/d, n=6) and the arterialinfusion group (group E, sustained infusion of rATG through femoral artery,1mg/kg/d,n=6). The general situation of recipients and the appearance of allografts wereobserved periodically after the transplantation operation, and the mean survival time ofallografts in each group was recorded. At the sixth day post operation, the tissuespecimen was taken from each group and observed under the optical microscope, themean rejection grade (MRG) score of each group was measured according to thedegree of rejection. At the day of-1,1,3,5,7,9,11post operation, serum of eachgroup was collected, and the concentration of IL-2was detected using enzyme-linkedimmune sorbent assay (ELISA).Results:The general situation of group A and group E was well, demonstrating a rapidlyincreasing body weight. Other groups demonstrated a slowly increasing body weightand suspected poisonous side effect. Group A showed an indefinite survival ofautografts. The mean survival time of group B, C, D, E was6.7±0.8、7.8±0.8、8.5±1.0and16.7±1.2days, respectively. There was a significant difference between each group(F=131.520, P＜0.01). The survival time of group E was significantly longer than theother groups (P＜0.01). The MRG score of group B, C, D, E at sixth day post operation was2.8±0.2、2.5±0.2、2.3±0.2and0.5±0.3, respectively. There was asignificant difference between each group (F=140.335, P＜0.01). The MRG score ofgroup E was significantly lower than the other groups (P＜0.01). The IL-2concentration in the serum of group B, C, D and E increased along with the passage oftime. The ratio of increase arranged in descending order: group B, group C, group Dand group E. The IL-2concentration in the serum of group E was significantly lowerthan group B, C and D (P＜0.05) at each time spot except the-1and1day postoperation.Conclusion:Compared with the method of intraperitoneal injection and intravenous infusion,arterial infusion of rATG can suppress the acute rejection of limb allograft moreeffectively with less impact on the general situation of recipient. Local arterial infusionof rATG may be more applicable to the immunosuppressive therapy after limballotransplantation.