Research on the Neuro-immunodulation Effect of Neuropeptides SP and CGRP on Rat Skin Allograft Model
|School||Central South University|
|Keywords||Allograft transplantation SP CGRP Neurogenicinflammation Neuro-immunomodulation|
Objective:To establish the allograft skin transplantation model of rat, and to study the effect of neuropeptides--substance P (SP) and calcitonin gene related peptide (CGRP)-on survival status of rat skin graft. Try to discuss the molecular mechanism of neuro-immunodulation.Methods:BALB/c and C57BL/6(B6)rats were used to establish the allograft skin transplantation model, between which have unmatched major histocompatibility complex(MHC), and divided into four groups according to the different interventions:(1) control group (only received an injection of the same amount of saline);(2) SP receptor antagonist;(3) CGRP receptor antagonist;(4) combined SP and CGRP antagonists. The control of autologous transplantation rats was set in each group.The survival statuses of skin graft were observed for25days. The skin grafts were used for further analysis. The expressions of SP, CGRP in skin graft were analyzed by enzyme linked immuno-histochemistry (IP) and reverse transcription polymerase chain reaction (PCR).Results:1. The allograft skin transplantation model of rat was established successfully. Surgery could cause different degree of neurogenic inflammation. 2. Compared to the allograft skin transplantation model, the skin grafts of autologous transplantation had significantly longer average survival times. In rats of allograft skin transplantation, comparing to group (1), the survival times of group (2) and (3) were significantly prolonged (p<0.05); and grafts from group (4) have the longest survival time (p<0.05).3. In comparison with autologous transplantation group, the expressions of SP and CGRP were higher in allograft groups (p<0.001). The expression of SP was down-regulated by SP receptor antagonist(p<0.001); and The expression of CGRP was down-regulated by CGRP receptor antagonist(p<0.001)Conclusions:1. Our study suggested that allograft skin transplantation can induce acute rejection, we can study the transplantation rejection and the neuro-immunodulation effect on this model.2. SP and CGRP have the effect of neuro-immunomodulation on allograft rejection. Blocking these effects can prolong the survival time of graft.