Estrogen is renoprotective via a nonreceptor-dependent mechanism after cardiac arrest in vivo.
Estrogen is renoprotective via a nonreceptor-dependent mechanism after cardiac arrest in vivo.
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DOI：
10.1097/aln.0b013e3181c98da9
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发表时间：
2010-02
期刊：
影响因子：
8.8
通讯作者：
Hurn PD
中科院分区：
文献类型：
--
作者：
Hutchens MP;Nakano T;Kosaka Y;Dunlap J;Zhang W;Herson PS;Murphy SJ;Anderson S;Hurn PD
女性严重缺血引起肾损伤的几率低于男性。在这项研究中，使用心脏骤停和心肺复苏来评估雌二醇是否通过雌激素受体（ER）依赖性机制具有肾脏保护作用。雄性和雌性 C57BL/6 和 ER 基因缺失小鼠经历 10 分钟的心脏骤停，然后进行心肺复苏。逮捕后 24 小时测量血清化学和肾脏体视学。雌激素不影响平均动脉压、局部肾皮质血流量和动脉血气。因此，女性肾脏受到保护（平均值±SEM：血尿素氮，65 ± 21 vs.149 ± 27 mg/dl，P = 0.04；肌酐，0.14 ± 0.05 vs. 0.73 ± 0.16 mg/dl，P = 0.01；坏死小管体积，7 ± 1% vs. 10 ± 0%，P = 0.04）。雌激素还可以减少肾损伤。在完整雌性 (n = 5)、卵巢切除/媒介物治疗 (n = 8) 和卵巢切除/雌激素治疗 (n = 8) 动物中，血液尿素氮为 65 ± 21、166 ± 28 和 50 ± 14 mg/dl (P = 0.002)；肌酐为 0.14 ± 0.05、0.74 ± 0.26 和 0.23 ± 0.27 mg/dl（P = 0.014）；肾小管坏死率分别为 2.5 ± 0.25%、12.0 ± 1.9% 和 5.0 ± 1.6% (P = 0.004)。在 ER-α 和 ER-β 基因缺失小鼠和对照组中，雌二醇减少了功能损伤（血尿素氮：雌二醇 117 ± 71，载体 167 ± 56，P = 0.007；肌酐：雌二醇 0.5 ± 0.5，载体 1.0 ± 0.4，P = 0.013），但雌二醇的作用是ER-α 或 ER-β 基因缺失小鼠之间没有差异。在雌二醇中添加 ICI 182,780 并没有改变损伤。对于女性来说，雌激素可以保护肾脏免于心脏骤停。雌二醇介导的肾脏保护不受 ER 缺失或阻断的影响。雌二醇在心脏骤停后具有肾脏保护作用。结果表明雌二醇的肾脏保护作用与 ER-α 和 ER-β 无关。
Severe ischemia induces renal injury less frequently in women than men. In this study, cardiac arrest and cardiopulmonary resuscitation were used to assess whether estradiol is renoprotective via an estrogen receptor (ER)-dependent mechanism. Male and female C57BL/6 and ER gene-deleted mice underwent 10 min of cardiac arrest followed by cardiopulmonary resuscitation. Serum chemistries and renal stereology were measured 24 h after arrest. Estrogen did not affect mean arterial pressure, regional renal cortical blood flow, and arterial blood gases. Hence, female kidneys were protected (mean ± SEM: blood urea nitrogen, 65 ± 21 vs.149 ± 27 mg/dl, P = 0.04; creatinine, 0.14 ± 0.05 vs. 0.73 ± 0.16 mg/dl, P = 0.01; volume of necrotic tubules, 7 ± 1% vs. 10 ± 0%, P = 0.04). Estrogen also reduced renal injury. In intact females (n = 5), ovariectomized/vehicle-treated (n = 8), and ovariectomized/estrogen-treated (n = 8) animals, blood urea nitrogen was 65 ± 21, 166 ± 28, and 50 ± 14 mg/dl (P = 0.002); creatinine was 0.14 ± 0.05, 0.74 ± 0.26, and 0.23 ± 0.27 mg/dl (P = 0.014); necrotic tubules were 2.5 ± 0.25%, 12.0 ± 1.9%, and 5.0 ± 1.6% (P = 0.004), respectively. In ER-α and ER-β gene-deleted mice and controls estradiol-reduced functional injury (blood urea nitrogen: estradiol 117 ± 71, vehicle 167 ± 56, P = 0.007; creatinine: estradiol 0.5 ± 0.5, vehicle 1.0 ± 0.4, P = 0.013), but the effect of estradiol was not different between ER-α or ER-β gene-deleted mice. Adding ICI 182,780 to estradiol did not alter injury. In women, kidneys were protected from cardiac arrest through estrogen. Estradiol-mediated renoprotection was not affected by ER deletion or blockade. Estradiol is renoprotective after cardiac arrest. The results indicate that estradiol renoprotection is ER-α and ER-β independent.