谷氨酰胺对脓毒症小鼠氧化应激损伤的保护作用研究

A study on protective effect of glutamine on oxidative stress injury in mice with sepsis

目的探讨谷氨酰胺是否可以减轻脓毒症小鼠的氧化应激损伤，从而为临床应用提供实验依据。方法按随机数字表采取完全随机化方法将5周龄雄性昆明小鼠分为对照组、模型组、谷氨酰胺组3组，每组10只。模型组与谷氨酰胺组腹腔注射内毒素5mL／kg制备脓毒症模型，对照组腹腔注射等量生理盐水。制模成功后，谷氨酰胺组即刻尾静脉注射丙氨酰谷氨酰胺注射液0．75gag，模型组和对照组尾静脉注射等量无菌生理盐水。6h后终止实验，眼眶取血后处死动物，取血清和肝、肾组织匀浆检测氧化应激指标超氧化物酶歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—Px）、丙二醛（MDA）。结果与对照组比较，模型组血清、肝、肾组织SOD活性、GSH—Px明显降低，MDA含量明显升高。与模型组比较，谷氨酰胺组血清、肝、肾组织SOD活性、GSH—Px明显升高，MDA含量明显降低[血清SOD（U／mL）：134．78±3．74比124．60±3．49，肝脏SOD（U／mg）：56．71±1．35比49．84±0．86，肾脏SOD（U／mg）：46．22±1．22比43．22±1．52；血清GSH—Px（U／mL）：325．15±21．86比267．04±13．5，肝脏GSH-Px（U／mg）：91．35±1．59比83．40±1．33，肾脏GSH—Px（U／mg）：136．08±O．58比132．97±0．74；血清MDA（tamol／L）：9．20±0．32比13．67±1．24，肝脏MDA（nmol／mg）：1．85±0．10比4．88±0．17，肾脏MDA（nmol／mg）：2．47±0．12比3．52±0．27，均P〈0．01]。结论脓毒症造成氧化应激与氧化损伤，使用谷氨酰胺可以提高抗氧化酶GSH—Px、SOD水平，增强抗氧化能力，减少脂质代谢产物MDA含量，减少有毒代谢产物，从而起到减少氧化应激损伤的作用。

Objective To explore whether glutamine can ameliorate oxidative stress injury in mice with sepsis in order to provide an experimental basis for clinical application. Methods Thirty 5-week old Qunming male mice were randomly divided into three groups： control, model and glutamine groups, 10 mice in each group. Lipopolysaccharide （LPS） 5 mL/kg was injected into intraperitoneal cavity to establish septic model in model and glutamine groups, and an equal amount of normal saline was injected into the cavity in control group. After the septic model was successfully established, propylene ammonia acyl-glutamine 0.75 g/kg was immediately injected through tail vein in the glutamine group, and an equal amount of sterile normal saline was injected into the vein in the model and control groups. After 6 hours, the experiment was terminated, the blood was collected from the orbital cavity and the animal was sacrificed; serum, liver and renal tissue homogenates were taken to detect the indexes of oxidative stress, superoxide dismutase （SOD）, glutathione peroxidase （GSH-Px）, and lipid metabolite malonaldehyde （MDA）. Results Compared with the control group, the levels of SOD activities and GSH-Px of serum and liver, kidney tissue in the model group were significantly loser, and the MDA content was significantly higher. Compared with the model group, the levels of SOD activities and GSH-Px of serum and liver, kidney tissue in the glutamine group were significantly higher, and the MDA content was significantly lower [SOD in the serum （U/mI,）： 134.78 ± 3.74 vs. 124.60 ± 3.49, SOD in the liver （U/mg）： 56.71 ± 1.35 vs. 49.84 ± 0.86, SOD in the kidney （U/rag）： 46.22 ± 1.22 vs. 43.22 ± 1.52; GSH-Px in serum （U/mL）： 325.15 ± 21.86 vs. 267.04 ± 13.5, GSH-Px in liver （U/mg）： 91.35 ± 1.59 vs. 83.40 ± 1.33, GSH-Px in kidney （U/mg）： 136.08±0.58 vs. 132.97±0.74; MDA in serum （Ixmol/L）： 9.20±0.32 vs. 13.67± 1.24, MDA in liver （nmol/mg）： 1.85 ± 0.10 vs. 4.88 ± 0.17, MDA in kidney （nmol/mg）： 2.47 ± 0.12 vs. 3.52 ± 0.27, all P 〈 0.01]. Conclusion Sepsis can cause oxidative stress and oxidative damage, glntamine not only can improve the levels of antioxidant enzymes of GSH-Px and SOD, enhance antioxidant capacity, reduce the MDA content of lipid metabolites, but also can reduce the toxic metabolites, so as glutamine has the effect of ameliorating oxidative stress injury.