Antus Balazs, Yao Yousheng, Song Erwei, Liu Shanying, Lutz Jens, Heemann Uwe
Department of Pathophysiology, Semmelweis Medical University, Budapest, Hungary.
Transpl Int. 2002 Oct;15(9-10):494-501. doi: 10.1007/s00147-002-0449-2. Epub 2002 Sep 20.
In the present study we investigated whether donor gender or the effects of sex hormones play the greater role in the development of chronic allograft nephropathy. Kidneys of male and female Fisher rats were orthotopically transplanted into castrated male Lewis recipients. Animals were treated with testosterone, estradiol, or vehicle and the kidneys were harvested 20 weeks after transplantation for histological, immunohistological, and molecular analysis. Testosterone treatment resulted in increased proteinuria and profound glomerulosclerosis, irrespective of donor gender. In addition, mRNA levels of transforming growth factor-beta1 (TGF-beta1) and platelet-derived growth factor-A and B (PDGF-A and B) chains were enhanced in these allografts. Estradiol reduced glomerulosclerosis and mononuclear cell infiltration in allografts of both genders that paralleled a decreased mRNA expression of TGF-beta1, PDGF-A and B. No donor gender-related differences were noted in vehicle-treated animals. Our findings demonstrate that sex hormones rather than donor gender have a significant impact on chronic allograft nephropathy.
在本研究中,我们调查了供体性别或性激素的作用在慢性移植肾肾病的发展中哪个发挥更大的作用。将雄性和雌性Fisher大鼠的肾脏原位移植到去势的雄性Lewis受体中。动物接受睾酮、雌二醇或赋形剂治疗,并在移植后20周采集肾脏进行组织学、免疫组织学和分子分析。无论供体性别如何,睾酮治疗都会导致蛋白尿增加和严重的肾小球硬化。此外,这些移植肾中转化生长因子-β1(TGF-β1)、血小板衍生生长因子-A和B(PDGF-A和B)链的mRNA水平升高。雌二醇减少了两性移植肾中的肾小球硬化和单核细胞浸润,这与TGF-β1、PDGF-A和B的mRNA表达降低平行。在接受赋形剂治疗的动物中未发现与供体性别相关的差异。我们的研究结果表明,性激素而非供体性别对慢性移植肾肾病有显著影响。