Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat
Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat
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DOI：
10.1152/jappl.2001.90.3.795
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发表时间：
2001-03-01
影响因子：
3.3
通讯作者：
Wilson, JX
中科院分区：
文献类型：
--
作者：
Armour, J;Tyml, K;Wilson, JX
脓毒症患者的血浆抗坏血酸浓度较低，微血管灌注受损。本实验的目的是确定抗坏血酸是否可以改善容量复苏脓毒症中的毛细血管功能。对雄性 Sprague-Dawley 大鼠进行盲肠结扎穿孔 (CLP)。术后24小时测量血浆和尿液中抗坏血酸浓度、平均动脉血压和指长伸肌中持续灌注的毛细血管密度。 CLP 导致血浆抗坏血酸浓度降低 50%（从 56 +/- 4 到 29 +/- 2 muM），尿液抗坏血酸浓度增加 1,000%（从 46 +/- 13 到 450 +/- 93 muM），平均动脉压降低 20%（从 115 +/- 2 到 91 +/- 2 mmHg），并降低 30%与时间匹配的对照相比，灌注毛细血管的密度（从 24 +/- 1 到 17 +/- 1 毛细血管/毫米）。 CLP 手术后立即静脉注射抗坏血酸（7.6 毫克/100 克体重）可增加血浆抗坏血酸浓度，并使血压和灌注毛细血管密度恢复至控制水平。体外实验表明，抗坏血酸（100 μM）可抑制细菌复制，并防止过氧化氢对培养的微血管内皮细胞造成损伤。这些结果表明，抗坏血酸在脓毒症期间随尿液流失，并且抗坏血酸丸剂可以预防脓毒症动物骨骼肌中的微血管功能障碍。我们的研究支持抗坏血酸可能对脓毒症综合征患者有益的观点。
Septic patients have low plasma ascorbate concentrations and compromised microvascular perfusion. The purpose of the present experiments was to determine whether ascorbate improves capillary function in volume-resuscitated sepsis. Cecal ligation and perforation (CLP) was performed on male Sprague-Dawley rats. The concentration of ascorbate in plasma and urine, mean arterial blood pressure, and density of continuously perfused capillaries in the extensor digitorum longus muscle were measured 24 h after surgery. CLP caused a 50% decrease (from 56 +/- 4 to 29 +/- 2 muM) in plasma ascorbate concentration, 1,000% increase (from 46 +/- 13 to 450 +/- 93 muM) in urine ascorbate concentration, 20% decrease (from 115 +/- 2 to 91 +/- 2 mmHg) in mean arterial pressure, and 30% decrease (from 24 +/- 1 to 17 +/- 1 capillaries/mm) in the density of perfused capillaries, compared with time-matched controls. A bolus of intravenous ascorbate (7.6 mg/100 g body wt) administered immediately after the CLP procedure increased plasma ascorbate concentration and restored both blood pressure and density of perfused capillaries to control levels. In vitro experiments showed that ascorbate (100 muM) inhibited replication of bacteria and prevented hydrogen peroxide injury to cultured microvascular endothelial cells. These results indicate that ascorbate is lost in the urine during sepsis and that a bolus of ascorbate can prevent microvascular dysfunction in the skeletal muscle of septic animals. Our study supports the view that ascorbate may be beneficial for patients with septic syndrome.