Department of Surgery, Rutgers-New Jersey Medical School, Newark, NJ, 07103, USA.
Hospital "October 1st", ISSSTE", 1669 National Polytechnic Institute Ave, Mexico City, Mexico.
Sci Rep. 2019 Jan 30;9(1):1012. doi: 10.1038/s41598-018-36298-z.
Sepsis is a leading cause of death in hospitalized patients. Many experimental treatments may have failed in clinical trials for sepsis, in part, because they focused on immune responses of healthy animals that did not mimic the metabolic settings of septic patients. Epidemiological studies show an association between metabolic and immune alterations and over 1/3 of septic patients are diabetic, but the mechanism linking these systems is unknown. Here, we report that metabolic fasting increased systemic inflammation and worsened survival in experimental sepsis. Feeding and administration of glucose in fasted mice activated the vagal tone without affecting blood pressure. Vagal stimulation attenuated hyperglycemia and serum TNF levels in sham but only hyperglycemia in splenectomized mice. Vagal stimulation induced the production of dopamine from the adrenal glands. Experimental diabetes increased hyperglycemia and systemic inflammation in experimental sepsis. Fenoldopam, a specific dopaminergic type-1 agonist, attenuated hyperglycemia and systemic inflammation in diabetic endotoxemic mice. These results indicate that glucose activates vagal control of hyperglycemia and inflammation in fasted septic mice via dopamine.
脓毒症是住院患者死亡的主要原因。许多针对脓毒症的实验性治疗方法在临床试验中都失败了，部分原因是它们专注于健康动物的免疫反应，而这些反应并不能模拟脓毒症患者的代谢环境。流行病学研究表明，代谢和免疫改变之间存在关联，超过 1/3 的脓毒症患者患有糖尿病，但这些系统之间的联系机制尚不清楚。在这里，我们报告称，代谢性禁食会增加全身炎症反应，并使实验性脓毒症患者的存活率降低。在禁食小鼠中喂养和给予葡萄糖会激活迷走神经张力，但不会影响血压。迷走神经刺激可减轻假手术小鼠的高血糖和血清 TNF 水平，但仅能减轻脾切除术小鼠的高血糖。迷走神经刺激可诱导肾上腺多巴胺的产生。实验性糖尿病会增加实验性脓毒症中的高血糖和全身炎症反应。芬纳多普，一种特定的多巴胺能 1 型激动剂，可减轻糖尿病内毒素血症小鼠的高血糖和全身炎症反应。这些结果表明，葡萄糖通过多巴胺激活迷走神经控制禁食脓毒症小鼠的高血糖和炎症。
