Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas.
Department of Pathology, University of Texas Medical Branch, Galveston, Texas.
Shock. 2023 May 1;59(5):810-819. doi: 10.1097/SHK.0000000000002108. Epub 2023 Mar 5.
In preclinical studies, the protective effects of female sex hormones and the immunosuppressive effects of male sex hormones were demonstrated. However, gender-related differences in multiorgan failure and mortality in clinical trials have not been consistently explained. This study aims to investigate gender-related differences in the development and progression of sepsis using a clinically relevant ovine model of sepsis. Adult Merino male (n=7) and female (n=7) sheep were surgically prepared with multiple catheters before the study. To induce sepsis, bronchoscopy instilled methicillin-resistant Staphylococcus aureus into sheep's lungs. The time from the bacterial inoculation until the modified Quick Sequential Organ Failure Assessment (q-SOFA) score became positive was measured and analyzed primarily. We also compared the SOFA score between these male and female sheep over time. Survival, hemodynamic changes, the severity of pulmonary dysfunction, and microvascular hyperpermeability were also compared. The time from the onset of bacterial inoculation to the positive q-SOFA in male sheep was significantly shorter than in female sheep. Mortality was not different between these sheep (14% vs. 14%). There were no significant differences in hemodynamic changes and pulmonary function between the two groups at any time point. Similar changes in hematocrit, urine output, and fluid balance were observed between females and males. The present data indicate that the onset of multiple organ failure and progression of sepsis is faster in male sheep than in female sheep, even though the severity of cardiopulmonary function is comparable over time. Further studies are warranted to validate the above results.
在临床前研究中，已经证明了女性性激素的保护作用和男性性激素的免疫抑制作用。然而，临床试验中多器官衰竭和死亡率的性别差异尚未得到一致解释。本研究旨在使用临床相关的绵羊脓毒症模型来研究脓毒症的发生和进展中的性别差异。成年美利奴公（n=7）和母（n=7）绵羊在研究前进行了多次导管手术准备。为了诱导脓毒症，支气管镜将耐甲氧西林金黄色葡萄球菌注入绵羊的肺部。测量并分析了从细菌接种到改良快速序贯器官衰竭评估（q-SOFA）评分阳性的时间。我们还比较了这些雄性和雌性绵羊随时间推移的 SOFA 评分。还比较了存活、血液动力学变化、肺功能障碍严重程度和微血管高通透性。雄性绵羊从细菌接种到 q-SOFA 阳性的时间明显短于雌性绵羊。这些绵羊的死亡率没有差异（14%对 14%）。两组在任何时间点的血液动力学变化和肺功能均无显著差异。在女性和男性之间观察到相似的血细胞比容、尿量和液体平衡变化。目前的数据表明，雄性绵羊多器官衰竭的发作和脓毒症的进展比雌性绵羊更快，尽管随着时间的推移心肺功能的严重程度相当。需要进一步的研究来验证上述结果。
