Alves Marcos Antonio, Guimarães Sérgio Botelho, Dias Daniel Aguiar, Vasconcelos Paulo Roberto Cavalcante de, Coelho Vicente de Paulo Martins, Vasconcelos Paulo Roberto Leitão de
Federal University of Ceará (UFC), Brazil.
Acta Cir Bras. 2005 Nov-Dec;20(6):445-9. doi: 10.1590/s0102-86502005000600009. Epub 2005 Nov 8.
To investigate the effects of l-alanyl-glutamine (Ala-Gln) intragastric administration upon blood and kidney metabolic parameters alterations in rats subjected to ischemia/reperfusion of hind limb.
Forty-eight male rats were randomized in 2 groups offered via gavage either saline 2.0 mL (G-1) or Ala-Gln solution 0.75 mgKg-1(G-2) once a day at 7 AM during 7 days. One-hour after the last gavage (Day 7) all rats were submitted to ether anesthesia, laparotomy and clamping of the left iliac artery for 3 h. Kidney and blood samples were collected at the end of ischemic period (3 h) and at 1-3-6 h during reperfusion period for metabolites (pyruvate, lactate, glucose and ketone bodies) enzymatic analysis. ATP was also assayed in kidney samples.
Lactacemia and ketonemia were significantly increased in Ala-Gln treated rats during reperfusion. Kidney pyruvate concentrations were significantly decreased and tissue lactate concentrations were significantly increased during reperfusion (1 h and 3 h) in G-2 rats compared with respective controls. Glucose, ATP and ketone bodies concentrations were significantly increased in the kidney in L-Ala-Gln treated rats at 3 hours after reperfusion as compared to respective controls.
Unilateral hind limb ischemia in L-Ala-Gln pre-treated rats may induce increased lactacemia and increased kidney lactate concentrations, indicating increased glycolytic activity in renal medulla and in other peripheral tissues. Higher ketonemia during reperfusion may reflect a possible increase in ketogenesis due to lower insulin plasma concentration hepatic signaling as a result of increased glucose oxidation in peripheral tissues, caused by the intra-gastric administration of glutamine dipeptide, suggesting also decreased insulin resistance.
研究胃内给予L-丙氨酰-谷氨酰胺(Ala-Gln)对后肢缺血/再灌注大鼠血液及肾脏代谢参数变化的影响。
48只雄性大鼠随机分为2组,在7天内每天上午7点经口灌胃给予2.0 mL生理盐水(G-1组)或0.75 mg/kg的Ala-Gln溶液(G-2组)。末次灌胃1小时后(第7天),所有大鼠接受乙醚麻醉、剖腹术并结扎左髂动脉3小时。在缺血期末(3小时)以及再灌注期的1、3、6小时采集肾脏和血液样本,进行代谢物(丙酮酸、乳酸、葡萄糖和酮体)的酶学分析。同时也对肾脏样本进行ATP检测。
再灌注期间,Ala-Gln处理的大鼠血乳酸和血酮水平显著升高。与各自对照组相比,G-2组大鼠在再灌注期间(1小时和3小时)肾脏丙酮酸浓度显著降低,组织乳酸浓度显著升高。再灌注3小时后,L-Ala-Gln处理的大鼠肾脏中葡萄糖、ATP和酮体浓度与各自对照组相比显著升高。
L-Ala-Gln预处理的大鼠单侧后肢缺血可能导致血乳酸升高以及肾脏乳酸浓度增加,表明肾髓质和其他外周组织的糖酵解活性增强。再灌注期间较高的血酮水平可能反映了由于胃内给予谷氨酰胺二肽导致外周组织葡萄糖氧化增加,进而引起肝信号通路中胰岛素血浆浓度降低,导致酮体生成可能增加,这也提示胰岛素抵抗降低。