Nöt Laszlo G, Marchase Richard B, Fülöp Norbert, Brocks Charlye A, Chatham John C
Department of Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Shock. 2007 Sep;28(3):345-52. doi: 10.1097/shk.0b013e3180487ebb.
We have previously shown that glucosamine administration resulted in higher cardiac output and improved tissue perfusion after trauma-hemorrhage with resuscitation in rats, which was associated with the increased levels of protein O-linked-N-acetylglucosamine (O-GlcNAc). The purpose of the study was to evaluate the effect of glucosamine on the survival, without resuscitation, in rats. Adult male rats underwent midline laparotomy and 55% of total blood volume was withdrawn for 25 min under isoflurane anesthesia. At the end of the hemorrhage period, 2.5 mL of 150 mM glucosamine or equivalent osmolarity of mannitol solution was injected intravenously for 10 min. The survival time, mean blood pressure, heart rate, and central body temperature were monitored continuously; then, the O-GlcNAc levels in heart, brain, liver, and muscle were measured by means of Western blot analysis. Glucosamine administration significantly increased the survival rate in comparison with mannitol administration (percentage of survival after 2 h, 47% vs. 20%; P < 0.05). The mean arterial pressure was significantly higher in the glucosamine group for 18 min after treatment. The protein O-GlcNAc levels, assessed 30 min after glucosamine treatment, were significantly increased in the heart, brain, and liver. These data demonstrate that i.v. glucosamine administration improves the survival rate after trauma-hemorrhage without resuscitation; this effect may be related to the glucosamine-induced increase in protein O-glycosylation. Furthermore, the increase in mean arterial pressure may suggest a vasoactive and/or positive inotropic effect of glucosamine in hypovolemic shock.
我们之前已经表明，在大鼠创伤性出血并复苏后，给予葡萄糖胺可导致心输出量增加和组织灌注改善，这与蛋白质O-连接-N-乙酰葡糖胺（O-GlcNAc）水平升高有关。本研究的目的是评估葡萄糖胺对未进行复苏的大鼠存活率的影响。成年雄性大鼠接受中线剖腹术，并在异氟烷麻醉下抽取55%的总血容量，持续25分钟。在出血期结束时，静脉注射2.5 mL 150 mM葡萄糖胺或等渗甘露醇溶液，持续10分钟。连续监测存活时间、平均血压、心率和中心体温；然后，通过蛋白质免疫印迹分析测量心脏、大脑、肝脏和肌肉中的O-GlcNAc水平。与给予甘露醇相比，给予葡萄糖胺显著提高了存活率（2小时后的存活率百分比，47%对20%；P<0.05）。治疗后18分钟，葡萄糖胺组的平均动脉压显著更高。在葡萄糖胺治疗30分钟后评估的蛋白质O-GlcNAc水平，在心脏、大脑和肝脏中显著升高。这些数据表明，静脉注射葡萄糖胺可提高创伤性出血未复苏后的存活率；这种作用可能与葡萄糖胺诱导的蛋白质O-糖基化增加有关。此外，平均动脉压的升高可能表明葡萄糖胺在低血容量性休克中具有血管活性和/或正性肌力作用。
