The Effect Of Glutamine And Arginine-enriched Enteral Nutrition On The Immune Function And The Protein Metabolism In Rats With Severe Head Injury

Background:The metabolic responses to severe head injury include hypermetabolism, hyperglycemia,acute phase response and immunosuppression,which often cause secondary infection.According to the literature,infection rate to severe head injury was about 50%～70%.In order to decrease the infection rate for severe-head-injured patients,it is important to improve the nutrition situation and to keep the immune function normal, because infection rate have close relationship with patients' nutrition.Clinically nutritional diets include element diet,non-element diet,module diet and special diet.In critically ill patients,there exist obstinate hypermetabolism,serious acid-base losing balance and disordered water-dielectric,which cause nutritional substrate utilization and low toleration, so the mode of traditional nutritional support improves less on patients' curative effect, resulting in malnutrition and immunosuppression of patients.With the development of clinical nutrition and advanced research of regulation metabolism,immunonutrition has been refered.A woking definition of 'Immunonutrition' may be 'modulation of the immune system,promotion of tissue repair,and improvement of patients'outcome,by nutrients or specific food items fed in amount above those normally encountered in diet'.The diet was named immune- enhancing diets(IEDs).The nutrients that have been studied most are glutamine,arginine,and the long fatty acids.In particular,glutamine and arginine have been best known of their pharmacological effect and little negative effect.Both laboratory and clinical studies have shown that glutamine and arginine can actively improve the immune function and the nutrition metabolism in burn,multiple trauma,and cancer patients. However,we are not awared of any reported study about whether the nutrients have beneficial effects on severe-head-injured patients.Objective:This study aims to investigate the effect of glutamine and arginine-enriched enteral nutrition on the immune function and the protein metabolism in rats with severe head injury,and try to afford a scientific evidence for clinical nutritional support.Methods:The model of severe head injury was established by local impact injury.72 male and female SD rats were randomly divided into five groups:normal control group(C group),enteral nutrition group(EN group),EN adding glutamine group(Gln group),EN adding arginine group(Arg group),EN adding glutamine and arginine group(Gln+Arg group).The rats in the C group were not injured.The other groups were fed nutritional diets which have the same nitrogen and calorie content four hours after injury.Rats were fed half of diet 71.49 Kcal/kg.d on the 1st day and total of diet 142.97Kcal/kg.d on the 2nd day.The peripheral blood samples of all rats were collected on the 3rd day and the 7th day. PMN phagocytosis rate was observed by phagocytosis Candida albicans count.CD4~+ cells and CD8~+ cells were analyzed by SABC.Serum IL-2(IL-2) level,insulin(INS). glucagons(GLU),and cortisol(Cor) concentrations were measured by radioimmunoassay (RIA).Contents of prealbumin(PA) and retinol-binding Protein(RBP) were examined by enzyme Linked Immunosorbent Assay(ELISA).Results were expressed as mean±standard error of the mean.Comparison of data intra-group was done by unpaired Independent t-test. The differences between groups were analyzed by one-way ANOVA.Data analysis was performed using the SPSS10.0 software package.P＜0.05 was considered statistically significant.Result:1.The model of severe head injury was established successfully2.CD4~+,CD4~+/CD8~+,IL -2 level,phagocytosis ratios in the EN group,Gln group, Arg group and Gln+Arg group were obviously lower than those in the C group(P＜0.01); also those ratios in the Gln group,Arg group,Gln +Arg group were noticeably higher than in the EN group(P＜0.01) on post-injury 3rd day.The cellular immune function of Gln group,Arg group and EN group showed a tendency of increase,but they were significantly lower than that in the C group(P＜0.01),and those of Gln group,Arg group were higher than that of EN group(P＜0.01) on post-injury 7th day.On each time point,there was no notable difference between the Gln group and the Arg group(P＞0.05).The Gln +Arg group had significantly more cellular immune function than the Gln group and the Arg group(P＜0.01) on post-injury 3rd day.The cellular immune function of the Gln +Arg group was recovering gradually,and it got close to normal level since the 7th day.3.Comparing with the C group,the PA and RBP content of EN group,Gln group, Arg group and Gln+Arg group decreased much more sharply(P＜0.01) and had no statistical significance between each other group(P＞0.05) on post-injury 3rd day.The PA and RBP content of EN group kept increasing steadily,but it was markedly lower than those of the C group(P＜0.01) on the post-injury 7th day.The content of each of the Gln group,the Arg group and the Glu+Arg group was higher than that of the EN group(P＜0.05～0.01),approached normal level(P＞0.05) and had no significant difference among the three groups(P＞0.05) on the 7th day.4.On the post-injury 3rd day,the Cor content in the EN group,the Gln group,the Arg group and the Gln+Arg group were significantly higher than that in the C group(P＜0.05～0.01),while the INS/GLU in these groups was sharply lower than those in the C group(P＜0.01).On each time point,the Cot content of EN group was noticeably higher than that of the other three groups(P＜0.05～0.01).There was no significant difference of the Cor content among the Gln group,the Arg group and the Gln+Arg group(P＞0.05) on the 3rd day,but that of Gln+Arg group was lower than the other two groups and approached normal level(P＞0.05) on the 7th day.In the Gln group and the Arg group,INS/GLU was higher than that in EN group(P＜0.05) on the post-injury 7th day.The INS /GLU of Gln+Arg group was greater than those of the other three experimental groups(P＜0.05～0.01),and the content of Cor and INS/GLU of the Gln group,the Arg group had no statistical significance on each time point(P＞0.05).Conclusion:1.Glutamine and arginine-enriched enteral nutrition might improve immuno-suppression, disordered protein metabolism and metabolic hormone in rats with severe head injury.2.Combined application of Gln with Arg in EN rats enhanced the rats' cellular immune function and metabolic hormone more than by giving either of them alone.3.Glutamine and arginine-enriched enteral nutrition of 7day or more had better curative effect.