Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?
Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock?
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DOI：
10.1186/s13054-015-1131-2
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发表时间：
2015-11-27
期刊：
影响因子：
--
通讯作者：
Natarajan R
中科院分区：
文献类型：
--
作者：
Carr AC;Shaw GM;Fowler AA;Natarajan R
严重的全身炎症反应导致严重的脓毒症和脓毒性休克，这是危重患者死亡的主要原因。脓毒性休克的特征是顽固性低血压，通常通过液体复苏和给予儿茶酚胺类血管加压药（如去甲肾上腺素）进行治疗。加压素也可以用来提高平均动脉压或减少去甲肾上腺素的剂量。内源性去甲肾上腺素和加压素分别由含铜酶多巴胺β-羟化酶和肽酰甘氨酸α-酰胺化单加氧酶合成。这两种酶都需要抗坏血酸作为最佳活性的辅因子。严重脓毒症患者存在维生素C缺乏症，临床前和临床研究表明，给予高剂量抗坏血酸盐可降低促炎生物标志物的水平，减轻器官功能障碍并改善血液动力学参数。可以想象，对患有维生素C缺乏症的脓毒症患者给予抗坏血酸盐可以改善内源性血管加压素的合成，从而改善对外源性血管加压素的需求。抗坏血酸依赖性血管加压素的合成是一种目前尚未充分研究的生化机制，抗坏血酸可作为严重脓毒症和脓毒性休克的辅助治疗。
Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamine β-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock.