Objective: To observe the change of postoperative fatigue in rats after the effect of branched chain amino acid(BCAA) and associated antagonists on central neurotransmitter 5-HT metabolic pathway, and to investigate the role of 5-HT in the development of postoperative fatigue syndrome(POFS).
Methods: Fifty SD rats were randomly divided into sham operation group(C group, n=10), model group(M group, n=10), L-type amino acid transporter inhibitor group(L group, n=10), 5-HT uptake inhibitor group(F group, n=10) and branched chain amino acids(B group, n=10). The rats in the C group and the M group were injected with normal saline, while other three groups were respectively injected with BCH, fluoxetine, BCAA(val:leucine:isoleucine=5:3:2), on preoperative 1 h, postoperative day 1, 2, 3, 4. The rats, except for those in the C group, underwent resection of 70% of the middle small intestine with end-to-end anastomosis. General status of the rats was observed before and after surgery. Morris water maze test, including the hidden platform test and search space test (detecting the learning ability of rats) and tail suspension test (detecting physical endurance of rats) were used to evaluate the degree of POFS from postoperative day 1 to day 7. Concentration of tryptophan(TRP), 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) in different position of brain(hippocampus, striatum, hypothalamus) of rats were measured by high performance liquid chromatography(HPLC) at postoperative day 8.
Results: As compared to the M group, other four groups showed better general condition and less fatigue. In the hidden platform test, M group showed the least time of crossing platform as compared to other four groups(all P<0.05). Meanwhile, M group and B group performed the longer incubation period than C group and L group(all P<0.05). In search space test, M group and B group showed less time of crossing platform, but there were no significant differences among the groups(all P>0.05). In tail suspension test, M group and F group showed lower score of physical strength than L group and B group(all P<0.05). Levels of TRP in the L, F, B groups were lower compared to the M group(all P<0.01) in brain tissue. The least concentration of striatum 5-HT was found in the C group but there were no significant differences among the M, L, F and B groups. Level of 5-HIAA in the M group, only in hypothalamus, was higher than that in the F group(P<0.05), but no significant differences between the M group and the L and B groups were found.
Conclusion: BCAA and associated antagonists (BCH, fluoxetine) can improve POFS by reducing the absorption of TRP that results in decreased synthesis of central 5-HT.