Wu Hao, Zhu Qiang, Liu Xuanyou, Hao Hong, Sun Zhe, Wang Meifang, Hill Michael A, Xu Canxia, Liu Zhenguo
Center for Precision Medicine and Division of Cardiovascular Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Department of Gastroenterology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Biology (Basel). 2022 Aug 4;11(8):1169. doi: 10.3390/biology11081169.
Inflammatory bowel disease (IBD) produces significant systemic inflammation and increases the risk of endothelial dysfunction and peripheral artery disease. Our recent study demonstrated that abdominal aortic endothelial cell function was impaired selectively in female mice with chronic colitis. This study aimed to test the hypothesis that experimental colitis leads to femoral artery endothelial cell dysfunction and impairs limb ischemia recovery in female mice. An experimental chronic colitis model was created in female C57BL/6 mice with dextran sodium sulfate (DSS) treatment. Unilateral hind limb ischemia was produced by femoral artery ligation. Limb blood perfusion, vascular density, tissue ROS levels, and plasma levels of proinflammatory cytokines were assessed. Femoral artery endothelium-dependent and -independent vasodilation of the contralateral limb were evaluated ex vivo using acetylcholine and nitroglycerin, respectively. As expected, the plasma levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, and IL-17, were significantly increased in the DSS-induced colitis model. However, ROS levels in the ischemic muscle tissues were not significantly increased in colitis model as compared to the controls. There were no significant changes in endothelium-dependent or -independent vasodilation of the femoral artery between colitis model and the control. Recovery of function and blood flow in the ischemic limb and capillary density in the ischemic gastrocnemius muscle were preserved in the colitis model as compared with the control. The data demonstrated that DSS-induced chronic colitis had no significant impact on femoral artery endothelial function or ischemic limb recovery in female mice.
炎症性肠病（IBD）会引发显著的全身炎症，并增加内皮功能障碍和外周动脉疾病的风险。我们最近的研究表明，在患有慢性结肠炎的雌性小鼠中，腹主动脉内皮细胞功能会选择性受损。本研究旨在验证实验性结肠炎会导致雌性小鼠股动脉内皮细胞功能障碍并损害肢体缺血恢复这一假说。通过用葡聚糖硫酸钠（DSS）处理雌性C57BL/6小鼠建立实验性慢性结肠炎模型。通过股动脉结扎造成单侧后肢缺血。评估肢体血液灌注、血管密度、组织活性氧水平和促炎细胞因子的血浆水平。分别使用乙酰胆碱和硝酸甘油在体外评估对侧肢体股动脉的内皮依赖性和非内皮依赖性血管舒张。正如预期的那样，在DSS诱导的结肠炎模型中，包括肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-6和IL-17在内的促炎细胞因子的血浆水平显著升高。然而，与对照组相比，结肠炎模型中缺血肌肉组织中的活性氧水平没有显著增加。结肠炎模型与对照组之间股动脉的内皮依赖性或非内皮依赖性血管舒张没有显著变化。与对照组相比，结肠炎模型中缺血肢体的功能和血流恢复以及缺血腓肠肌中的毛细血管密度得以保留。数据表明，DSS诱导的慢性结肠炎对雌性小鼠的股动脉内皮功能或缺血肢体恢复没有显著影响。
