甘氨酸和丙酮酸对于局部缺血再灌注后的全身性保护作用

目的 肠系膜上动脉缺血/再灌注可引起小肠局部损伤,甚至休克和心肺功能障碍。丙酮酸和甘氨酸已被证实对缺血再灌注损伤的局部组织器官有保护作用。本文研究其对小肠缺血再灌注之后全身血流动力学以及心肺功能等的影响。方法 采用雄性SD大鼠,麻醉后建立血流动力学监测,建立肠系膜上动脉缺血90 min、再灌注120 min的模型。24只大鼠随机分为4组：丙酮酸组（再灌注前给予丙酮酸50 mg/kg,n=6）;甘氨酸组（再灌注前给予甘氨酸20 mg/kg,n=6）;林格组（再灌注前给予林格氏液1 mL,n=6）;假手术对照组（n=6）。术中记录平均动脉压、心脏指数、肺动脉压等,并估计循环血管阻力。采集动脉血进行血气分析和心肌标志物检测。观察结束后处死大鼠,取小肠、心脏、肺脏、肝脏进行组织学观察。结果 丙酮酸和甘氨酸均能有效稳定血流动力学参数,维持较好的心功能。其中甘氨酸组复苏所需晶体体积显著少于对照组。丙酮酸、甘氨酸对代谢性酸中毒的抑制作用明显优于林格氏液（P<0.01）。甘氨酸组的小肠、肺、心、肝病理评分和中性粒细胞浸润明显低于林格组（P<0.01）,但仍高于假手术组（P<0.01）。丙酮酸组、甘氨酸组CKMB、肌钙蛋白I水平低于林格组,但仍高于假手术组（P<0.01）。结论 丙酮酸和甘氨酸能在严重的局部缺血再灌注之后稳定全身循环状态,改善休克的复苏效果,既可减轻局部组织器官的缺血再灌注损伤,又可保护心肺等器官的功能。

Protective effects of glycineand pyruvate after intestinal ischemia/reperfusion

Objective Superior mesenteric artery （SMA） ischemia/reperfusion （I/R） may cause severe shock and cardiac and lung injury. Pyruvate and glycine have been demonstrated to protect the local tissue after I/R. In this study the effects of these substances on hemodynamics and cardiopulmonary functions are investigated. Methods After anesthesia male SD rats were operated to establish hemodynamic monitoring. Then SMA ischemia was applied for 90 minutes, by reperfusion for 120 minutes. During the reperfusion sufficient Ringer solution was infused for resuscitation. Totally 24 rats were divided into 4 groups： a control group with the sham operation （sham, n=6）; SMA I/R with pyruvate （50 mg/kg, n=6） or glycine （20 mg/kg, n=6） or equal amount of Ringer （1 mL, n=6） given before reperfusion. Mean arterial pressure （MAP）, cardiac index （CI）, pulmonary artery pressure （PAP） etc. were recorded and systemic vascular resistances （SVR） were calculated during the whole operation. Arterial blood samples were taken for gas analysis and myocardial markers. At the end of observation, the rats were sacrificed and the intestine, heart, lung, liver were harvested for histology study. Results Pyruvate and glycine both effectively stabilized the hemodynamic parameters and facilitated the maintenance of CI with less crystal volume for resuscitation than Ringer group. In Pyruvate and glycine groups the pathological score and neutrophil sequestration of the intestine, lung, heart and liver were significantly lower than Ringer group （P<0.01） but still higher than Sham group （P<0.01）. Metabolic acidosis was also inhibited in Pyruvate and Glycine groups than Ringer group （P<0.01）. Creatine kinase-MB and troponin I in Glycine and Pyruvate groups elevated less than the Ringer group but still more than the Sham group （P<0.05）. Conclusion After SMA I/R, pyruvate and glycine could improve the hemodynamic performances, facilitate the resuscitation for circulatory shock, and protect the local tissue against I/R injury and cardiopulmonary functions.