*Laboratory of Cardiovascular Surgery and Circulation Pathophysiology (LIM-11), Heart Institute (InCor), Medical School, São Paulo, Brazil †Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Shock. 2017 Oct;48(4):477-483. doi: 10.1097/SHK.0000000000000873.
Intestinal ischemia and reperfusion (I/R) triggers a systemic inflammatory response characterized by leukocyte mobilization from the bone marrow, release of cytokines to the circulation, and increased microvascular permeability, leading to high mortality. Females have shown attenuated inflammatory response to trauma when compared with males, indicating a role for female sex hormones in this process. Here, we have evaluated the effect of estradiol on the local gut injury induced by I/R in male rats. I/R was induced by the clamping of the superior mesenteric artery for 45 min, followed by 2 h of reperfusion. A group received 17β-estradiol (280 μg/kg, i.v., single dose) at 30 min of ischemia. Morphometric analysis of the gut showed I/R induced a reduction of villous height that was prevented by estradiol. White blood cells, notably granulocytes, were mobilized from the circulation to the intestine by I/R, which was also prevented by estradiol treatment. Groups had the intestine wrapped in a plastic bag to collect intestinal fluid, where leukocytes count, TNF-α, and IL-10 levels were increased by I/R. Serum chemokines (CINC-1, MIP-1α, MIP-2), ICAM-1 expression in the mesenteric tissue, and neutrophils spontaneous migration measured in vitro were also increased after I/R. Estradiol treatment reduced leukocytes numbers and TNF-α on intestinal fluid, serum chemokine release and also downregulated MIP-1α, MIP-2 gene expression, and spontaneous in vitro neutrophil migration. In conclusion, estradiol blunts intestinal injury induced by I/R by modulating chemokines release and leukocyte trafficking.
肠缺血再灌注（I/R）引发全身性炎症反应，其特征为骨髓中白细胞动员、细胞因子释放入血循环以及微血管通透性增加，导致高死亡率。与男性相比，女性在创伤后表现出炎症反应减弱，表明女性性激素在这一过程中发挥作用。在此，我们评估了雌二醇对雄性大鼠 I/R 诱导的局部肠道损伤的影响。I/R 通过夹闭肠系膜上动脉 45 分钟，然后再灌注 2 小时来诱导。一组在缺血 30 分钟时给予 17β-雌二醇（280μg/kg，静脉注射，单次剂量）。肠道形态计量分析显示，I/R 导致绒毛高度降低，而雌二醇可预防这种降低。白细胞，特别是粒细胞，通过 I/R 从循环动员到肠道，雌二醇治疗也可预防这种动员。各组将肠道包裹在塑料袋中以收集肠液，I/R 会导致肠液中白细胞计数、TNF-α 和 IL-10 水平升高。血清趋化因子（CINC-1、MIP-1α、MIP-2）、肠系膜组织中 ICAM-1 表达以及体外测定的中性粒细胞自发迁移在 I/R 后也增加。雌二醇治疗可减少肠液中的白细胞计数和 TNF-α、血清趋化因子释放，并下调 MIP-1α、MIP-2 基因表达以及体外中性粒细胞自发迁移。总之，雌二醇通过调节趋化因子释放和白细胞迁移来减轻 I/R 诱导的肠道损伤。
