Harward T R, Coe D, Souba W W, Klingman N, Seeger J M
Department of Surgery, University of Florida College of Medicine, Gainesville 32610-0286.
J Surg Res. 1994 Apr;56(4):351-5. doi: 10.1006/jsre.1994.1054.
Intestinal ischemia/reperfusion (I/R) causes formation of reactive oxygen intermediates (ROI) which lead to mucosal cell injury. Glutathione (GSH), an ROI scavenger, protects tissues from ROI-mediated cell injury. Since GSH biosynthesis is partially dependent on glutamine (Gln) levels, we tested the hypothesis that intravenous Gln infusion will assist in maintaining mucosal cell GSH levels and decrease membrane lipid peroxidation during intestinal I/R. The external jugular vein of male Sprague-Dawley rats was cannulated and infused with normal saline (NS) at 2 cc/hr. After 3 days, matched pairs of rats received either NS alone or NS+ 3% Gln for an additional 24 hr. Next, mucosal GSH levels were measured after a sham I/R in 6 rats and after either 30 or 60 min of ischemia/60 min of reperfusion in a group of 8 and 12 rats, respectively. Finally, conjugated diene (CD), a byproduct of membrane lipid peroxidation, was measured following 60 min of ischemia/60 min of reperfusion in a separate group of 12 rats. Control rats had the highest GSH levels and there was no difference between NS vs NS + 3% Gln rats (2.50 +/- 0.48 vs 2.50 +/- 0.43, P = NS). With 30 and 60 min of ischemia/60 min of reperfusion, GSH levels were significantly lower in NS-infused rats compared to those in NS + 3% Gln-infused rats (30 min: 1.54 +/- 0.14 vs 1.80 +/- 0.16, P < 0.05; 60 min: 1.27 +/- 0.15 vs 1.52 +/- 0.20, P < 0.04). In addition, CD levels were lower in NS + 3% Gln-infused rats compared to those in NS alone-infused rats (5.58 +/- 0.87 vs 7.94 +/- 0.55, P < 0.04). In conclusion, Gln supplementation partially maintains gut GSH levels during bowel I/R, which in turn lessens I/R-induced cell membrane lipid peroxidation.
肠道缺血/再灌注（I/R）会导致活性氧中间体（ROI）的形成，进而引发黏膜细胞损伤。谷胱甘肽（GSH）作为一种ROI清除剂，可保护组织免受ROI介导的细胞损伤。由于GSH的生物合成部分依赖于谷氨酰胺（Gln）水平，我们检验了以下假设：静脉输注Gln有助于在肠道I/R期间维持黏膜细胞的GSH水平，并减少膜脂质过氧化。将雄性Sprague-Dawley大鼠的颈外静脉插管，以2 cc/小时的速度输注生理盐水（NS）。3天后，将配对的大鼠分别单独接受NS或NS + 3% Gln，持续24小时。接下来，在6只大鼠进行假I/R后，以及在一组8只和12只大鼠分别经历30或60分钟缺血/60分钟再灌注后，测量黏膜GSH水平。最后，在另一组12只大鼠经历60分钟缺血/60分钟再灌注后，测量膜脂质过氧化的副产物共轭二烯（CD）水平。对照大鼠的GSH水平最高，NS组与NS + 3% Gln组大鼠之间无差异（2.50 ± 0.48对2.50 ± 0.43，P =无显著差异）。在经历30和60分钟缺血/60分钟再灌注后，输注NS的大鼠的GSH水平显著低于输注NS + 3% Gln的大鼠（30分钟：1.54 ± 0.14对1.80 ± 0.16，P < 0.05；60分钟：1.27 ± 0.15对1.52 ± 0.20，P < 0.04）。此外，输注NS + 3% Gln的大鼠的CD水平低于单独输注NS的大鼠（5.58 ± 0.87对7.94 ± 0.55，P < 0.04）。总之，补充Gln在肠道I/R期间可部分维持肠道GSH水平，进而减轻I/R诱导的细胞膜脂质过氧化。
