Petrat F, Drowatzky J, Boengler K, Finckh B, Schmitz K J, Schulz R, de Groot H
Institute für Physiologische Chemie, Universitätsklinikum Essen, Essen, Deutschland.
Eur Surg Res. 2011;46(4):180-7. doi: 10.1159/000324393. Epub 2011 Mar 31.
Glycine at high doses is known to protect the small intestine against ischemia-reperfusion (I/R) injury. Here, we studied whether glycine at low clinically applicable doses has a protective effect.
In series 1, intestinal I/R was induced in male Wistar rats by occlusion (90 min)/reopening (120 min) of the superior mesenteric artery. Glycine was intravenously infused for 30 min before ischemia (pre-ischemic infusion), and once again from 30 min before until 60 min after reperfusion. Total glycine doses applied over the 120-min infusion were 5, 10, 20, and 75 mg glycine/kg. In series 2, pre-ischemic blood plasma glycine concentrations were determined under the conditions of series 1.
In series 1, attenuation of I/R injury was comparable at 10, 20, and 75 mg glycine/kg, but less at 5 mg/kg (as indicated by less intestinal hemorrhages and better preserved mean arterial blood pressure, among other signs). In series 2, pre-ischemic blood plasma glycine concentrations increased with increasing glycine doses from 280 to 330, 340, 380, and 680 μM, respectively.
These results demonstrate that even at a dose 50 times lower than previously applied - and at only slightly elevated plasma concentrations - glycine provides full protection against I/R injury of the small intestine.
已知高剂量甘氨酸可保护小肠免受缺血再灌注(I/R)损伤。在此,我们研究了临床适用的低剂量甘氨酸是否具有保护作用。
在系列1中,通过肠系膜上动脉闭塞(90分钟)/再开放(120分钟)在雄性Wistar大鼠中诱导肠I/R。在缺血前30分钟静脉输注甘氨酸(缺血前输注),并在再灌注前30分钟至再灌注后60分钟再次输注。在120分钟输注期间应用的总甘氨酸剂量为5、10、20和75毫克甘氨酸/千克。在系列2中,在系列1的条件下测定缺血前血浆甘氨酸浓度。
在系列1中,10、20和75毫克甘氨酸/千克时I/R损伤的减轻程度相当,但在5毫克/千克时减轻程度较小(表现为肠出血较少和平均动脉血压保存较好等迹象)。在系列2中,缺血前血浆甘氨酸浓度随着甘氨酸剂量的增加而增加,分别从280增加到330、340、380和680μM。
这些结果表明,即使剂量比以前应用的低50倍,且血浆浓度仅略有升高,甘氨酸也能完全保护小肠免受I/R损伤。