大鼠异种心脏移植中P选择素和细胞间粘附分子-1表达的意义

Effect of immunosuppression on the expression of P-selectin and ICAM-1 in hamster to rat concordant cardiac xenotransplantation

目的探讨大鼠异种心脏移植中P选择素和细胞间粘附分子-1（ICAM-1）表达的意义。方法建立金黄地鼠到SD大鼠的异种异位（腹部）心脏移植模型，然后将模型大鼠随机分为4组：对照组术后不采取任何治疗措施；环孢素A组（CsA组）于手术当天起每天腹腔注射CsA 10mg／kg；脾切除组于手术当天切除脾脏；CsA联合脾切除组于手术当天切除脾脏，每天腹腔注射CsA 10mg／kg。观察每组移植心脏的存活时间，定时和发生排斥反应时切取移植心组织，进行病理学检查，并以免疫组化方法观察移植物中P选择素和ICAM-1的表达。结果CsA联合脾切除组移植心脏存活时间为（34．2±8．98）d，较对照组、CsA组和脾切除组明显延长（P〈0．05）。CsA联合脾切除组术后1～5d移植物中未见明显病理改变；7、14d时移植心脏组织结构清晰，未见血栓及出血；30d时移植心脏组织结构基本正常，排斥反应级别为I～Ⅱ；其它三组的病理改变明显，对照组于术后1～2d、脾切除组及已A组于术后4～7d发生延迟性排斥反应。CsA联合脾切除组术后各观察时点移植心脏组织中均未见P选择素和ICAM-1表达，其它三组的P选择素和ICAM-1均呈阳性。结论异种移植发生延迟性排斥反应时，P选择素和ICAM-1均有表达，可以作为判断异种移植免疫抑制治疗效果的指标之一。

Objective To study the role of the expression of P-selectin and intercellular adhesion molecule-1 （ICAM-1） in hamster to rat concordant cardiac xenotransplantation. Methods Intraabdominal cardiac transplantation was performed by using SD rats as recipients of Golden Syrian hamster hearts. The rats were divided into 4 groups randomly： group I （n = 15）, unmodified recipients were used as control; group II （n = 15）, splenectomy at day 0; group Ⅲ （n = 15）, the rats were treated with cyclosporine A （CsA） 10 mg/kg every day from day 0; group IV （n = 15）, splenectomy in combined with CsA. The survival ot hamster hearts was observed in each group. The xenograft was harvested at rejection and scheduled time in accordance with the experimental design, and analyzed for histology. The expression of P-selectin and ICAM-1 was detected by immunohistochemistry in xenograft after xenotransplantation. Results The mean survival time of the xenograft in group IV was 34. 20 ± 8. 98 days, which was significantly longer in groups I, II and III （P〈0. 05）. The xenograft showed seldom pathological changes in group IV from day 1 to day 5. On the day 7 and 14, histological changes of xenograft （group IV） exhibited excellent preservation of myocardial architecture,without intravascular thrombosis and hemorrhage. On the day 30, the architecture of long-term survival xenograft was almost normal, and the grade of its rejection was Ⅰ-Ⅱ. In contrast, the xenografts in other groups showed some significant pathological changes, which were rejected on the day 1-2 （group Ⅰ） or day 4-7 （groups Ⅱ, Ⅲ） after the xenotransplantation. The expression of P-selectin and ICAM-1 was not detected in the xenograft in group IV on every observing point, but increased in cardiac xenografts in other groups. Conclusion The expression of P-selectin and ICAM-1 in xenografts was increased during delayed xenograft rejection, which is of value in judging the effect of immunosuppression in xenotransplantation.