The Research On Immunopathology Of Xenograft In Hyperacute And Acute Vascular Rejection

Objective:Research on the survival time and the changes of immunopathology of the xenografts afterα1,3GT and NF-κB expression are inhibited by RNA interference using lentiviral vectors.Methods:Establish a mouse-to-rat heterotopic cardiac xenotransplantatic model (donor heart transplanted to the right side of the neck in rat) by Using modified cuff technique described by Heron. The models were divided into 5 groups respectively according to different target genes of RNAi as followings:the control group, lentivirus vector without interference sequence group, RNAi al,3GT group, RNAi NF-κB group, RNAiα1,3GT+NF-KB group. Each group had eight pairs. The survival time of donor hearts in each group were monitored. The levels of C3, IgM, IgG, NK, macrophages, ICAM-1 of donor hearts were examined by the method of SABC.Result:The mean survival time of xenografts in the control group, lentivirus vector without interference sequence group, RNAiα1,3GT group, RNAi NF-κB group, RNAiα1,3GT+NF-KB group were(32±2.5)h, (31±2.5)h, (51±4.0)h, (31±1.8)h, (53±7.3)h respectively. No differences were found among the control group, lentivirus vector without interference sequence group, and RNAi NF-κB group(p>0.05). In RNAiα1,3GT and RNAiα1,3GT+NF-κB group, survival time of the xenografts were prolonged (p<0.05). No differences were found between RNAiα1,3GT group and RNAi al,3GT+NF-KB group (p>0.05).C3,IgM,IgG were obviously deposited in the xenografts of the control group, lentivirus vector without interference sequence group, RNAi NF-κB group, without differences(p>0.05). The deposition of C3, IgM, IgG in RNAiα1,3GT group and RNAiα1,3GT+NF-κB group were less than control group, lentivirus vector without interference sequence group, RNAi NF-κB group(p<0.05), but without differences between the above groups(p>0.05). The infiltration of NK, macrophages and ICAM-1 expression can be found in the control group, lentivirus vector without interference sequence group, RNAi NF-κB group, without difference(p>0.05). The infiltration of NK, macrophages and ICAM-1 in RNAiα1,3GT group and RNAiα1,3GT+NF-κB group were more than the control group, lentivirus vector without interference sequence group, RNAi NF-κB group(p<0.05). the RNAi al,3GT+NF-κB group was less than the RNAi al,3GT group (p<0.05).Conclusion:Xenoantigen Gala(1,3)Gal plays an important role in mouse to rat cardiac xenotransplantation. Xenografs may survive longer by decreasing the expression of Gala(1,3)Gal by RNAi. Deposition of IgM, IgG and C3 in the xenografts were decreased, as well as natural killer cells, macrophages, ICAM-1 in the xenografts were increased, meaning a change from HAR to AVR. The characteristics of the mouse to rat xenograft rejection are HAR and AVR co-existenced and HAR plays more. RNAi NF-κB can make the infiltration of Macrophages and natural killer cells decreasing, and the expression of ICAM-1 in the xenografts decreasing too, contributing to restraining AVR.