mdr-1基因骨髓造血干细胞移植诱导大鼠肝移植免疫耐受

Induction of immune tolerance of rat liver transplantation via transplantation of mdr-1 gene bone marrow stem cells

目的探讨mdr-1基因骨髓造血干细胞移植诱导肝移植术后免疫耐受的可行性及其可能机制。方法选用雄性Wistar大鼠30只为肝移植供体,另选雌性SD大鼠20只为异基因肝移植受体,随机分为mdr-1基因骨髓造血干细胞移植联合肝移植组(A组)和单纯肝移植组(B组)。雌性Wistar大鼠10只为同基因肝移植受体(C组)。比较A、B两组大鼠肝移植术后1周生存率、生存状况、生存时间,以及移植肝脏的病理变化。结果 C组大鼠生存时间均达60 d以上,A组为(31.2±4.9)d,明显高于B组[(12.1±4.7)d],差异有统计学意义(P<0.05)。B组病理组织切片可见中、重度急性排斥反应,肝内单核细胞浸润较为明显,主要集中在汇管区;A组移植肝内组织损伤程度明显减轻;C组基本无排斥反应,接近正常肝组织。结论 mdr-1基因骨髓造血干细胞可明显减轻大鼠肝移植后免疫排斥反应。

Objective To discuss the feasibility and possible mechanism of mdr-1 gene bone marrow stem cell transplantation inducing immune tolerance after liver transplantation. Methods Thirty male Wistar rats were used as the liver transplantation donors and 20 female SD rats as allogeneic liver transplantation recipients. The rats were randomly divided into two groups, ie, Group A （treated with mdr-1 gene Hematopoietic stem cell transplantation plus liver transplantation） and Group B （sole liver transplanta- tion）. Ten female Wistar rats were use as syngeneic liver transplantation recipients（Group C）. The survival rate, survival status, survival time and the pathological changes of the transplanted liver at one week after transplantation were compared between groups. Results The rats in Group C survived for over 60 days. The rats in Group A survived for（31.2±4.9） days,which was significantly higher than （12.1 ± 4.7） days in Group B（P〈0.05）. Histologic results showed moderate to severe acute rejection, obvious intrahepatic inflammatory cell infiltration mainly in the portal area in Group B. Ttissue injury of the transplanted liver was significantly alleviated in Group A. There was little rejection in Group C,which was close to the normal liver tissue. Conclusion The results of the study indicate that transplantation of mdr-1 gene bone marrow stem cells can markedly alleviate the immunological rejection after rat liver transplantation.