Li Xujiong, Li Wei, Wang Tao, Li Yan, Zhao Li
Department of Exercise Physiology, Beijing Sport University, Beijing, China.
Department of Physiology, Changzhi Medical College, Changzhi, China.
Front Immunol. 2024 Dec 18;15:1466615. doi: 10.3389/fimmu.2024.1466615. eCollection 2024.
Endotoxemia is a common issue for patients with biliary obstruction. The lung is the most affected organ by endotoxins. Exercise training can alleviate lipopolysaccharide (LPS)-induced lung inflammation and resveratrol has biological effects similar to exercise. In this study, we evaluated the protective effects of exercise preconditioning, resveratrol, and their combination on LPS-induced lung injury and mortality in rats with obstructive jaundice.
Endotoxemia was simulated in rats by common bile duct ligation (CBDL) and intraperitoneal injection of low-dose LPS. The treatment groups were pretreated with exercise and/or resveratrol to assess their effects on lung injury and mortality. Immunohistochemistry, immunofluorescence, and ELISA were subsequently used to evaluate the impact of exercise and/or resveratrol on inflammation in lung tissue and bronchoalveolar lavage fluid.
We found that even in the early stages, compared to sham-LPS rats, low-dose LPS induced excessive systemic inflammatory responses in CBDL rats, as evidenced by a significant increase in TNF-α and IL-6, severe lung inflammation, lung injury, and higher mortality rates, indicating that cholestasis increased rats' susceptibility to endotoxins. Exercise training reduced neutrophil infiltration in the lungs of model rats and IL-6 levels in bronchoalveolar lavage fluid. Both exercise training and resveratrol exhibited synergistic effects in reducing macrophage accumulation in lung tissues, lowering TNF-α and IL-6 levels in the lungs, and decreasing TNF-α concentration in bronchoalveolar lavage fluid. Additionally, exercise and combined interventions both significantly increased the expression of IL-10. The interventions induced a marked improvement in lung tissue pathological damage and lung edema in model rats and prolonged the survival time of rats with obstructive jaundice.
This study demonstrates that exercise preconditioning and/or resveratrol can significantly reduce rats' susceptibility to endotoxins after CBDL and alleviate lung injuries through their anti-inflammatory effects, thereby decreasing the mortality risk.
内毒素血症是胆道梗阻患者的常见问题。肺是受内毒素影响最严重的器官。运动训练可减轻脂多糖（LPS）诱导的肺部炎症，白藜芦醇具有与运动相似的生物学效应。在本研究中，我们评估了运动预处理、白藜芦醇及其组合对LPS诱导的梗阻性黄疸大鼠肺损伤和死亡率的保护作用。
通过胆总管结扎（CBDL）和腹腔注射低剂量LPS在大鼠中模拟内毒素血症。对治疗组进行运动和/或白藜芦醇预处理，以评估其对肺损伤和死亡率的影响。随后使用免疫组织化学、免疫荧光和ELISA来评估运动和/或白藜芦醇对肺组织和支气管肺泡灌洗液中炎症的影响。
我们发现，即使在早期阶段，与假LPS大鼠相比，低剂量LPS在CBDL大鼠中诱导了过度的全身炎症反应，TNF-α和IL-6显著增加、严重的肺部炎症、肺损伤以及更高的死亡率证明了这一点，表明胆汁淤积增加了大鼠对内毒素的易感性。运动训练减少了模型大鼠肺部的中性粒细胞浸润以及支气管肺泡灌洗液中的IL-6水平。运动训练和白藜芦醇在减少肺组织中的巨噬细胞积聚、降低肺组织中的TNF-α和IL-6水平以及降低支气管肺泡灌洗液中的TNF-α浓度方面均表现出协同作用。此外，运动和联合干预均显著增加了IL-10的表达。这些干预显著改善了模型大鼠的肺组织病理损伤和肺水肿，并延长了梗阻性黄疸大鼠的存活时间。
本研究表明，运动预处理和/或白藜芦醇可显著降低CBDL后大鼠对内毒素的易感性，并通过其抗炎作用减轻肺损伤，从而降低死亡风险。
