靶向CD40的shRNA干扰抗大鼠异体肢体移植急性排斥反应的实验研究

Resistance to acute rejection by shRNA interference from CD40 costimulatory molecule in limb allotransplantation in rats

目的探讨靶向CIM0的RNA干扰对大鼠异体肢体移植急性排斥反应的影响。方法以纯系SD大鼠为供体，纯系Wistar大鼠为受体，行同种异体右后肢移植。27只大鼠肢体移植后随机分为三组，A组：注射入梭华-Sofast—siCD40—2／pSilencer载体复合物600μL；B组：注射Sofast-pSilencer4．1-CMV neo空载体复合物600μL；C组：注射生理盐水600μL，以上均通过阴茎背静脉注射。观察移植物排斥反应征象及存活情况，并于第7天对产生免疫耐受大鼠进行混合淋巴细胞反应，同时进行组织学检查。结果与B、C组相比，A组移植物发生排斥反应的时间及存活时间均显著延长，差异有统计学意义（P〈0．01）（〉13d），未见排斥反应征象；B、C组均于术后近期发生排斥反应。A组大鼠对供体的淋巴细胞呈现低反应性，移植的供体同系大鼠的肢体得以存活。结论术后不应用免疫抑制剂的情况下，靶向CD40的shRNA干扰可以抗大鼠异体肢体移植急性排斥反应。

Objective To study the resistance to acute reaction in composite tissue allotransplantation by shRNA interference from CD40 costimulatory molecule in rat lymphocytes. Methods The inbred SD rats were chosen as donors and inbred Wistar rats as recipients. Twenty-seven recipients were divided into 3 groups randomly after allogeneie leg transplantation. On the day after transplantation, rats in group A were injected with 600 μL of Sofast-siCD40-2/pSilencer, rats in group B received 600 μL of Sofast-pSilencer 4. 1-CMV neo, and rats in group C received injection of 600 μL of sodium chloride. The survival and rejection to grafts were observed. The rats which survived 7 days after operation were given the test of mixed lymphocyte reaction （MIR）. Results The mean survival time of limb allografts in group A was obviously longer than that in the other two groups（ P 〈 0. 01） . Rejection to grafts was not observed in group A, but rejection emerged shortly after transplantation in the other two groups. Rats in group A had a low reaction to the donors＇ lymphocytes. Conclusion Without any immnosuppressants, shRNA interference from CD40 eostimulatory molecule can resist acute rejection in limb allotransplantation in rats.