Carbon monoxide-bound hemoglobin vesicles ameliorate multiorgan injuries induced by severe acute pancreatitis in mice by their anti-inflammatory and antioxidant properties.
Carbon monoxide-bound hemoglobin vesicles ameliorate multiorgan injuries induced by severe acute pancreatitis in mice by their anti-inflammatory and antioxidant properties.
复制标题
DOI：
10.2147/ijn.s118185
复制
发表时间：
2016
影响因子：
8
通讯作者：
Maruyama T
中科院分区：
文献类型：
--
作者：
Nagao S;Taguchi K;Sakai H;Yamasaki K;Watanabe H;Otagiri M;Maruyama T
一氧化碳（CO）作为影响抗炎和抗氧化活性的可能治疗剂而引起人们的关注。此前，CO 结合血红蛋白囊泡 (CO-HbV) 被开发为基于纳米技术的 CO 供体，并在体外和体内检查了其作为临床适用的 CO 载体的安全性和治疗潜力。在本研究中，使用补充了缺乏胆碱的乙硫氨酸饮食喂养的继发性远端器官损伤模型小鼠，检查了 CO-HbV 对重症急性胰腺炎的治疗效果。与盐水和 HbV 相比，CO-HbV 治疗显着降低了急性胰腺炎模型小鼠的死亡率。生化和组织学评估清楚地表明，CO-HbV 通过抑制胰腺组织中全身促炎细胞因子的产生、中性粒细胞浸润和氧化损伤来抑制急性胰腺炎。有趣的是，CO-HbV 还减少了对肝脏、肾脏和肺等远端器官的后续损伤。这可能是由于中性粒细胞浸润组织受到抑制以及随后氧化损伤的增强。相比之下，O2 结合的 HbV（CO-HbV 的非活性形式）对胰腺炎和远端器官损伤均无效，这证实 CO 直接导致 CO-HbV 对急性胰腺炎的保护作用。这些发现表明，CO-HbV 具有 CO 的抗炎和抗氧化特性，因此对急性胰腺炎引起的多器官损伤发挥优异的保护作用。
Carbon monoxide (CO) has attracted attention as a possible therapeutic agent for affecting anti-inflammatory and antioxidant activities. Previously, CO-bound hemoglobin vesicle (CO-HbV) was developed as a nanotechnology-based CO donor, and its safety profile and therapeutic potential as a clinically applicable carrier of CO were examined in vitro and in vivo. In the present study, the therapeutic efficacy of CO-HbV against severe acute pancreatitis was examined with secondary distal organ-injured model mice that were fed with a choline-deficient ethionine-supplemented diet. A CO-HbV treatment significantly reduced the mortality of the acute pancreatitis model mice compared to saline and HbV. Biochemical and histological evaluations clearly showed that CO-HbV suppressed acute pancreatitis by inhibiting the production of systemic proinflammatory cytokines, neutrophil infiltration, and oxidative injuries in pancreatic tissue. Interestingly, CO-HbV also diminished the subsequent damage to distal organs including liver, kidneys, and lungs. This could be due to the suppression of neutrophil infiltration into tissues and the subsequently enhanced oxidative injuries. In contrast, O2-bound HbV, the inactive form of CO-HbV, was ineffective against both pancreatitis and distal organ injuries, confirming that CO was directly responsible for the protective effects of CO-HbV in acute pancreatitis. These findings suggest that CO-HbV has anti-inflammatory and antioxidant characteristics of CO and consequently exerts a superior protective effect against acute pancreatitis-induced multiorgan damage.