性别对大鼠心脏移植模型中同种异体移植排斥反应的影响。

Influence of gender on allograft rejection in a rat heart transplant model.

作者信息

Takami H, Backer C L, Crawford S E, Zales V R, Mavroudis C

机构信息

Division of Cardiovascular-Thoracic Surgery, Children's Memorial Hospital, Chicago, IL 60614, USA.

出版信息

J Heart Lung Transplant. 1995 May-Jun;14(3):529-36.

PMID:7654736

Abstract

BACKGROUND

Clinical studies have reported increased rejection in female heart transplant recipients. Conflicting data exist as to whether rejection is increased with male donors or female donors in these female recipients.

METHODS

We investigated in this study allograft rejection in four sets of gender combinations with and without immunosuppression with the use of a heterotopic rat heart transplant model: male donor heart to female recipient, female donor heart to female recipient, male donor to male recipient, and female donor to male recipient. To examine the possible effect of androgens as an immunosuppressant, we orchiectomized a group of male recipient rats before transplantation. The rats that were not immunosuppressed were evaluated for length of graft survival (palpation). In the immunosuppressed rats (cyclosporine, 10 mg/kg x 7 days) in each gender combination half of the grafts were evaluated for length of survival (palpation) and half for cellular rejection grade at day 14 (microscopy).

RESULTS

When rats that underwent transplantation were not immunosuppressed, no difference in graft survival time was found among the four sets of gender combinations. With immunosuppression, median graft survival time was 23 days in female recipients versus 32 days in male recipients (p < 0.05). Mean cellular rejection grade at day 14 was 2.95 +/- 0.7 in female recipients and 0.8 +/- 0.4 in male recipients (p < 0.01). No significant difference was found in graft survival time or cellular rejection grade with respect to donor gender. The graft survival times and cellular rejection grades of the male rats undergoing orchiectomy were not different from those of normal male recipients (p = NS). Cyclosporine levels on day 7 in both male and female recipients were high, female levels (1039 +/- 411 ng/ml) were less than male levels (2029 +/- 379 ng/ml) (p < 0.01).

CONCLUSIONS

Female recipients of heterotopic rat heart transplants had shorter graft survival time and increased cellular rejection as compared with male recipients. Donor gender had no influence on graft survival or cellular rejection grade. Orchiectomy had no influence on graft survival time or grade of rejection. Results of this model suggest that female recipients may require increased immunosuppression and rejection surveillance, regardless of donor gender.

摘要

背景

临床研究报告称女性心脏移植受者的排斥反应增加。关于在这些女性受者中，男性供体还是女性供体导致的排斥反应增加，存在相互矛盾的数据。

方法

在本研究中，我们使用异位大鼠心脏移植模型，研究了四组性别组合在有或无免疫抑制情况下的同种异体移植排斥反应：雄性供体心脏移植给雌性受体、雌性供体心脏移植给雌性受体、雄性供体移植给雄性受体以及雌性供体移植给雄性受体。为了研究雄激素作为免疫抑制剂的可能作用，我们在移植前对一组雄性受体大鼠进行了去势手术。对未进行免疫抑制的大鼠评估移植物存活时间（触诊）。在每种性别组合的免疫抑制大鼠（环孢素，10mg/kg×7天）中，一半移植物评估存活时间（触诊），另一半在第14天评估细胞排斥分级（显微镜检查）。

结果

未进行免疫抑制的移植大鼠中，四组性别组合的移植物存活时间没有差异。进行免疫抑制时，雌性受体的移植物中位存活时间为23天[公式]，而雄性受体为32天（p<0.05）。第14天雌性受体的平均细胞排斥分级为2.95±0.7，雄性受体为0.8±0.4（p<0.01）。关于供体性别，移植物存活时间或细胞排斥分级没有显著差异。接受去势手术的雄性大鼠的移植物存活时间和细胞排斥分级与正常雄性受体没有差异（p=无显著性差异）。雄性和雌性受体在第7天的环孢素水平都很高，雌性水平（1039±411ng/ml）低于雄性水平（2029±379ng/ml）（p<0.01）。