Effects of lipopolysaccharide on the tryptophan-kynurenine metabolic pathway
10.3760/cma.j.issn.1674-6554.2015.08.001
- VernacularTitle:脂多糖对大鼠脑内犬尿氨酸代谢通路的影响
- Author:
Lihong ZHANG
;
Pei JIANG
;
Huande LI
;
Hualin CAI
;
Lingjuan CAO
- Publication Type:Journal Article
- Keywords:
Lipopolysaccharide;
Depression;
Indoleamine 2,3-dioxygenase;
Tryptophan;
Kynurenine
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2015;24(8):673-676
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of lipopolysaccharide(LPS) on the tryptophan-kynurenine(TRP) metabolic pathway in rat brains and provide new evidence for the relationship between inflammation and depression.Methods Rats in LPS group were given a single dose of 3.5 mg/kg LPS.while the rats in control group were given the same dosage of saline.The dialysis in ventro-hippocampus were collected by microdialysis within 8 hours and then the TRP,KYN and KA were detected by LC-MS/MS.And the expression of indoleamine 2,3-dioxygenase was detected by Western-blot.Results The level of TRP((550.15± 107.96) pmol/L) and KYN ((337.95±62.73) pmol/L) showed a time-dependent increase after administration LPS 4 h compared with the control group(TRP (368.38±59.31) pmol/L,KYN (172.80±43.96) pmol/L),while KA level in the circulation exhibited a trend to decrease,especially at 7 h ((3.47±0.62) pmol/L,P<0.05).The ratio of KYN/TRP significantly increased at about 5 h (0.69±0.11,P< 0.05),and an ratio of KA/KYN (0.02±0.00) was dramatically decreased after administering LPS 4 h compared with the control group (0.05±0.01)(P<0.05).Most of the analytes showed more dramatic changes around 4 h to 8 h.LPS group(1.48±0.37) increased the protein expression of indoleamine 2,3-dioxygenase compared with the control group(1.00±0.24) (P<0.01).Conclusions LPS may cause tryptophan metabolic abnormalities and accelerate the way of kynurenine metabolism,leading to decreased the kynurenic acid status.