Ischemia-reperfusion (I/R) injury, an inevitable result of kidney transplantation, triggers early inflammatory events that affect graft viability. Evidence from human transplantation and preclinical models of I/R suggests that a female hormonal environment positively influences the ability to recover from ischemic injury. However, the mechanisms behind these effects remain mostly unexplored. Here, we studied the influence of sex on pro-inflammatory mediators involved in the pathophysiology of acute I/R injury in male, female, and female ovariectomized (OVX) Wistar rats that underwent unilateral renal ischemia for 45 min, followed by 24 h of reperfusion. We found improved renal function, reduced cytokine expression, and decreased infiltration of myeloperoxidase-positive cells in females after I/R, when compared to their male and female OVX counterparts. Remarkably, citrullination of histone H3 was exacerbated in serum and renal tubules of females after I/R. In contrast, we observed lower levels of citrullinated histone H3 in male and female OVX rats in response to I/R, mostly in neutrophil extracellular traps. Our results demonstrate that female sex promotes renal I/R tolerance by attenuating pro-inflammatory mediators involved in I/R-induced damage.

缺血再灌注（I / R）损伤是肾脏移植的必然结果，它会触发早期炎症事件，从而影响移植物的生存能力。来自人类移植和I / R临床前模型的证据表明，女性激素环境对缺血性损伤的恢复能力产生积极影响。但是，这些作用背后的机制仍未得到充分探索。在这里，我们研究了性别对参与雄性，雌性和雌性去卵巢（OVX）Wistar大鼠的急性I / R损伤的病理生理过程的促炎性介质的影响，这些大鼠分别进行了45分钟的单侧肾缺血，随后24小时的再灌注。我们发现I / R后女性的肾功能改善，细胞因子表达降低和髓过氧化物酶阳性细胞浸润减少，与男性和女性OVX对手相比。值得注意的是，I / R后女性血清和肾小管中组蛋白H3的瓜氨酸化加剧。相比之下，我们观察到雄性和雌性OVX大鼠中对I / R响应的瓜氨酸化组蛋白H3含量较低，主要是在嗜中性粒细胞外陷阱中。我们的结果表明，女性可以通过减弱参与I / R诱导的损伤的促炎性介质来促进肾脏对I / R的耐受性。