Effects Of Glutamine On The Expression Of Oxidative Stress And NF-κB In The Livers Of Rats With Nonalcoholic Fatty Liver Disease

Objectives:To establish a model of nonalcoholic fatty liver disease(NAFLD) rat fedwith high fat diet. To investigate the effect of glutamine on changing theexpression of oxidative stress and NF-κB in the development of NAFLD, andexplore the NAFLD possible pathogenesis.Methods:Thirty-six male SD rats were randomly divided into normal control group(Cgroup), model group fed with high fat diet(M group).Three groups have two timepoints: feeding for8and12weeks,6ones at each time point. T group weresubjected to oral glutamine(1g/kg.d) administration at initiate experiment stage,while rats in the C and M group were subjected to oral saline (1ml/d). Check onthe weight of rats weekly. Measure the serum ALT, AST, TG and TC, and detectthe lever of GSH，TNF-αand MDA in the liver. Liver histopathologic evaluationwas performed by hematoxylin-eosin staining. The expression of NF-κB p65in the liver were measured by immunohistochemical staining.Results:(1) The body weight was gradually increased in M and T group than in Cgroup (P<0.05). Glutamine administration showed no obvious difference atweight gain compared with M group (P>0.05). The liver index was elevated in Mgroup (P<0.05), and intensified with time. Glutamine could greatly reduce theliver index in time-dependent way(P<0.05).(2)Compared with the C group at the same experimental period, liver functi-on and serum lipid in the M group were increased, but those of T group wereimproved. (3) Hepatic steatosis in the M group at week8th (M1) was mild or moderateand hepatic steatosis in the model group at week12th (M2) wasmoderate orsevere. Hepatic steatosis in M group was more severe than Cgroup（P＜0.05）,while glutamine administration significantly attenuated hep-aticpathological changes compared to M group at the same experimental period(P<0.05).(4)TNF-α, MDA levels in the liver homogenates were significantly higher inM group than in C group, especially at week12(P<0.05). Glutamine administrationcould greatly lower TNF-α and MDA levels (P<0.05). But GSH levels in the liverhomogenates of M group were gradually decreased than C group (P<0.05).Glutamine administration could greatly maintain GSH levels (P<0.05).(5) NF-κB protein65expression in liver were progressively increased in Mgroup (P<0.05), and were significantly higher than C group (P<0.05). There weresignificantly reduced in T group, compared with M group (P<0.05).Conclusions:High fat diet can successfully induce NAFLD model. Compared with Cgroup,MDA and TNF-αlever were increased, NF-κB p65were upregulated andGSH lever was reduced in M group. But all indexes were improved by glutamineadministration. Glutamine probably have therapeutic effect on improving hepaticsteatosis on NAFLD, which may be relative with reducing the lever of oxidativestress and inhibiting NF-κB expression in the liver.