精氨酸强化全胃肠外营养对肠屏障功能的保护

Protective effects of arginine enriched total parenteral nutrition on the gut barrier function

目的:采用幼兔全胃肠外营养动物模型,观察精氨酸强化全胃肠外营养对肠屏障功能的保护作用。方法:实验于2004-06/2005-05在上海交通大学医学院附属新华医院中心实验室完成。选择新西兰幼兔24只,随机数字表法分为3组。正常对照组右颈静脉结扎后自由饮食,其余两组经右颈静脉插入硅胶管;标准全胃肠外营养组每天输注标准全胃肠外营养液(735kJ/kg,200mL/kg),精氨酸强化全胃肠外营养组输注精氨酸占总热量2%的等氮等热量的全胃肠外营养液。7d后分别取血浆及回肠标本进行检测:①肠黏膜形态学改变。②肠菌移位率。③血浆D-乳酸含量。⑤血浆和回肠组织一氧化氮含量、回肠组织一氧化氮合酶活性和诱导型一氧化氮合酶mRNA表达。结果:纳入动物24只,均进入结果分析。①肠黏膜在标准全胃肠外营养组明显变薄、萎缩(P<0.01),而精氨酸强化全胃肠外营养组肠黏膜的萎缩较标准全胃肠外营养组明显减轻[黏膜厚度分别为(333.12±36.29),(279.13±49.01)μm,P<0.05],与正常对照组差异无显著性意义(P>0.05)。②标准全胃肠外营养组细菌移位率明显高于正常对照组(分别为62.5%,0,P<0.01),精氨酸强化全胃肠外营养组肠菌移位率较标准全胃肠外营养组显著降低(分别为12.5%,62.5%,P<0.05),与正常对照组差异无显著性意义(P>0.05)。③精氨酸强化全胃肠外营养组血浆D-乳酸含量较标准全胃肠外营养组明显降低[分别为(3.886±1.243),(7.218±1.470)mg/L,P<0.01],但较正常对照组仍偏高(P<0.05)。④精氨酸强化全胃肠外营养组回肠组织的一氧化氮含量、一氧化氮合酶活性和诱导型一氧化氮合酶mRNA表达强度较标准全胃肠外营养组有显著增加[一氧化氮含量分别为(1.163±0.123),(0.901±0.252)μmol/L;一氧化氮合酶活性分别为(85.92±16.92),(67.76±15.57)μkat/g;诱导型一氧化氮合酶mRNA表达分别为71.0±10.1,60.4±9.4,P<0.05],与正常对照组差异无显著性意义(P>0.05)。各组血浆中一氧化氮含量差异无显著性意义(P>0.05)。结论:精氨酸对维持肠黏膜形态和功能的完整性具有重要作用,其作用机制与肠道诱导型一氧化氮合酶产生的一氧化氮有关,添加适量外源性的精氨酸具有改善全胃肠外营养所致小肠黏膜损伤的作用。

AIM： To investigate the protective effects of arginine enriched total parenteral nutrition （TPN） on the gut barrier function by using young rabbit TPN models. METHODS： The experiment was conducted in the Central Laboratory of Xinhua Hospital Affiliated to the Medical College of Shanghai Jiaotong University from June 2004 to May 2005. Twenty-four young rabbits were selected and randomly divided into 3 groups, Animals in the control group freely took food and water after ligation of the right jugular vein, while animals in the standard TPN group and arginine enriched TPN group received standard TPN solution （735 kJ/kg,200 mL/kg） and arginine enriched （accounted for 2% of total energy） TPN respectively after silastic catheter insertion through the fight jugular vein into the superior vena cava. Seven days after TPN administration, the plasma and ileum were collected for the following tests： ① Intestinal morphological changes. ②Incidence of bacterial translocation. ③ D-lactic acid level in plasma. ④NO levels in plasma and in ileum, NOS activity and iNOS mRNA expression in ileum. RESULTS： A total of 24 enrolled animals were involved in the analysis of results.① The mucosal thickness in the standard TPN group was significantly thinner and shrank （P 〈 0.01）, while that in the arginine enriched TPN group was remarkably relieved than that in the standard TPN group [the mucosal thickness were （333.12±36.29） and （279.13±49.01） pan respectively,P 〈 0.05], which was not significantly different with that in the control group （P 〉 0.05）. ② The incidence of bacterial translocation in the standard TPN group was significantly higher than that in control group （which were 62.5% and 0 respectively, P 〈 0.01）, while that in the argnine enriched TPN group significantly decreased more than that in the standard TPN group （12.5% ,62.5% ,P 〈 0.05）, and there were no significant differences with the control group （P 〈 0.05）, ③ The plasma D-lactic acid level in the arginine enriched TPN group was significantly lower than that in the standard TPN group （3.886±1.243）,（7.218±1.470）mg/L, P 〈 0.01）, while it was still higher than that in the control group （P〈0.05）. ④ The NO level, NOS activity and iNOS mRNA expression in ileum in the arginine enriched TPN group were significantly higher than those in the standard TPN group [NO： （1.163±0.123）, （0.901±0.252）μmol/L;NOS activity： （85.92±16.92）,（67.76±15.57）μkat/g;The iNOS mRNA expression： 71.0±10.1,60.4±9.4, P 〈 0.05], which were not significantly different with those in the control group （P 〈 0.05）. There were no significantly differences among the three groups in plasma NO level （P 〉 0.05）. CONCLUSION＂ Arginine plays an important role in maintaining the integrity and function of gut barrier, the action mechanism of which is related with the NO produced by iNOS. Administration with proper arginine can ameliorate the injury in intestinal mucous membrane induced by TPN.