FcγRIIb基因修饰树突状细胞对大鼠原位肝移植排斥反应的影响

Effects of FcγRIIb gene modified dendritic cells on immune tolerance of rat orthotopic Liver transplantation

目的研究FcγRIIb基因修饰树突状细胞对大鼠原位肝移植术后肝功能及病理排斥反应的影响。方法利用基因克隆技术构建含Lewis大鼠FcγRIIb基因的重组慢病毒表达载体TRE-FcγRIIb。分别包装TRE-FcγRIIb表达病毒与TET-on可诱导病毒,用其共感染DA大鼠骨髓来源未成熟树突状细胞并检测FcγRIIb的表达。将供体DA大鼠与受体Lewis大鼠按照体重进行配对后随机分为三组,三组均行DA-Lewis的大鼠原位肝移植术。对照组(A组)不给予任何预处理。环孢素A组(B组)术后第2天开始给予环孢素A处理。FcγRIIb基因修饰未成熟树突状细胞组(C组)术前1d供体大鼠静脉注射FcγRIIb修饰的DA大鼠骨髓来源的未成熟树突状细胞(1×10^(6)细胞)。术后第7天分别取血和肝脏检测肝功能和肝脏病理变化。结果C组术后第7天肝功能异常明显低于对照组(P<0.05);C组术后第7天肝脏病理排斥反应明显低于对照组(P<0.05)。对照组中的大鼠平均存活天数为12.8d;B组的大鼠平均存活天数为65.3d;C组的大鼠平均存活天数为58.5d。结论FcγRIIb基因修饰未成熟树突状细胞可以降低大鼠原位肝移植术后肝功能异常,减轻术后大鼠肝脏急性排斥反应。

Objective To study the effects of FcγRIIb gene modified dendritic cells on liver function and rejection after orthotopic liver transplantation in rats.Methods The recombinant lentivirus expression vector TRE-FcγRIlb containing Lewis rat FcγRIIIb gene was constructed by gene cloning technique.TRE-FcγRIIb expression virus and TET-omn regulatory vinus were packaged and o-infected with immature dendritie cells derived from DA rat bone marow.The expression of FcγRIIb was delected.Donor rats DA and recipient Lewis were paired according to body weight and then randomly divided into three groups.The control group(group A)did not receive any pretreatment.The Lewis rats in group B were treated with cyclosporin A on the 2nd day after liver TX.Immature dendritic cells derived from bone marrow of DA rats were injected intravenously one day before liver TX in FcγRIIb gene modified inmature dendritie cells(1×10^(6)cells)group(group C).Blood and liver tssue were biopsied 7 days after operation to detect liver function and pathological changes.Results The abnormal liver function in FcyRllb gene modified immature dendritie cells group(group C)was signifieantly lower than that of control group 7 days after opratinn(Pc005).and the liver patholngieal rjeetin of FcγRIIh gene mdified immature dendritie cells group(group C)was significantly lower than that of control group 7 days afer operation(P<0.05).The average survival days of rats in the control group was 12.8 days;the average survival days of rats in the cyclosporin A group was 65.3 days;the average survival days of rats in the FcyRIIb gene-modified immature dendritic cell group was 58.5 days.Conclusion FcγRIIb gene modified immature dendritic cells can ameliorate liver dysfunction and acute liver rejection after orthotopic liver transplantation.