Department of Surgery, University of Pennsylvania, Philadelphia, PA.
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA.
Transplantation. 2022 Nov 1;106(11):2166-2171. doi: 10.1097/TP.0000000000004194. Epub 2022 Oct 21.
There is increasing evidence that estrogen is responsible for improved outcomes in female kidney transplant recipients. Although the exact mechanism is not yet known, estrogen appears to exert its protective effects by ameliorating ischemia-reperfusion injury (IRI). In this study, we have examined whether the beneficial effects of exogenous estrogen in renal IRI are replicated by therapy with any one of several selective estrogen receptor modulators.
C57BL/6 adult mice underwent standardized warm renal ischemia for 28 min after being injected with the selective estrogen receptor modulators, raloxifene, lasofoxifene, tamoxifen, bazedoxifene, or control vehicle (dimethyl sulfoxide), at 16 and 1 h before IRI. Plasma concentrations of blood urea nitrogen and creatinine were assessed 24, 48, 72, and 96 h post-IRI. Tissue was collected 30 d postischemia for fibrosis analysis using Sirius Red staining.
Raloxifene treatment in female mice resulted in significantly lower blood urea nitrogen and creatinine after IRI and significantly lower fibrosis 30 d following IRI.
Raloxifene is protective against both acute kidney injury and fibrosis resulting from renal IRI in a mouse model.
越来越多的证据表明雌激素可改善女性肾移植受者的预后。尽管确切的机制尚不清楚，但雌激素似乎通过改善缺血再灌注损伤（IRI）来发挥其保护作用。在这项研究中，我们研究了外源性雌激素对肾 IRI 的有益作用是否可以通过使用几种选择性雌激素受体调节剂中的任何一种来复制。
C57BL/6 成年小鼠在接受选择性雌激素受体调节剂雷洛昔芬、拉索昔芬、他莫昔芬、巴多昔芬或对照溶剂（二甲亚砜）注射后，在 IRI 前 16 小时和 1 小时进行标准化的温热肾缺血 28 分钟。在 IRI 后 24、48、72 和 96 小时评估血尿素氮和肌酐的血浆浓度。在缺血后 30 天收集组织，用天狼星红染色进行纤维化分析。
在雌性小鼠中，雷洛昔芬治疗可显著降低 IRI 后的血尿素氮和肌酐，并显著降低 IRI 后 30 天的纤维化。
雷洛昔芬可预防小鼠模型中肾 IRI 引起的急性肾损伤和纤维化。
