Alanyl-glutamine down-regulates iNOS and TNF-? expression in injured intestinal mucosa induced by oral FK506
- VernacularTitle:丙氨酰-谷氨酰胺下调口服他克莫司损伤的肠黏膜组织中iNOS和TNF-?的表达(英文)
- Author:
Yunle WAN
;
Lihua WU
;
Songfeng YU
;
Jing JIN
;
Qinghong KE
;
Shusen ZHENG
- Publication Type:Journal Article
- Keywords:
Tacrolimus;
Intestinal mucosa;
Alanyl-glutamine;
Nitric-oxide synthase;
Tumor necrosis factor
- From:
Chinese Journal of Pathophysiology
1989;0(05):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To investigate the effects of alanyl-glutamine (Ala-Gln) on expression of iNOS and TNF-? in injured intestinal mucosa induced by oral tacrolimus(FK506). METHODS: Twenty-four BALB/c mice were randomized to receive orally 0.2 mL of normal saline solution ( groupⅠ), 0.2 mL of FK506 in a dose of 0.1 mg/kg (groupⅡ) or 1.0 mg/kg (groupⅢ), and orally high-dose FK506 (0.2 mL, 1.0 mg/kg) plus intraperitoneal injection of Ala-Gln (0.5 g/kg )(groupⅣ),respectively. Damages of intestinal mucosa were determined by pathological examination. Intestinal mucosal permeability was analysed by FITC-dextran fluorescence assay. Expression of iNOS and TNF-? in intestine was detected by RT-PCR and Western blotting.RESULTS: Severe damage on the villi and increased intestinal permeability were observed in high-dose FK506 treated mice according to scanning electron microscopy and FITC-dextran flux respectively. The erosion and increased intestinal permeability were significantly alleviated by Ala-Gln treatment. Transcription of iNOS mRNA and TNF-? mRNA, which was up-regulated in high-dose FK506 treated group, was also markedly down-regulated in mice combined with Ala-Gln-treatment. A significantly increased expression of iNOS and TNF-? protein was found in the high-dose FK506 treated mice, while small amounts of these proteins were identified in the Ala-Gln-treated group.CONCLUSION: FK506 could induce a significant impairment of intestinal mucosa morphologically, which might be associated with up-regulated expression of iNOS and TNF-? in small intestinal mucosa. Subsequently, the intestinal permeability is increased. Ala-Gln has a strong protective effect on FK506-induced intestinal barrier dysfunction, probably relates to the down-regulation of iNOS and TNF-? expression.
