ABSTRACT
AIM: To explore the protective effect and mechanism of dexmedetomidine on intestinal mucosal barrier injury in septic rats. METHODS: Forty eight SD rats were randomly divided into four groups (n=12): sham operation group (sham group), sepsis group (sepsis group), sepsis + dexmedetomidine group (DEX group), and sepsis + DEX + HIF-1ɑ inhibitor Bay87-2243 (Bay87-2243 group). Sepsis model was established by cecal ligation and perforation (CLP). The rats in both DEX and Bay87-2243 groups were given 30 μg/kg of DEX intraperitoneally 30 minutes before CLP and 2 hours after CLP; while the rats in Bay87-2243 group received oral gavage of Bay87-2243 (9 mg/kg) for 3 days before CLP. The other groups were intraperitoneally injected and orally with the same amount of normal saline. The HIF-1ɑ and the tight junction protein (tight junction protein, TJs) was detected by western blot; the plasma concentrations of diamine oxidase (DAO), intestinal fatty acid binding protein (FABP2) and D-lactic acid (D-LAC) were detected by ELISA; the morphological changes of intestinal mucosa were detected by HE staining. RESULTS: DEX significantly increased the expression level of HIF-1ɑ (P<0.05) on intestinal mucosa in rats with sepsis injury (P<0.05), thus ameliorated intestinal mucosal pathological injury, reduced Chiu's score (P<0.05), decreased intestinal mucosal permeability (P<0.05), and up-regulated TJs protein expression (P<0.05). Moreover, effect on sepsis induced intestinal mucosal injury of DEX was reversed by HIF-1ɑ Bay87-2243. CONCLUSION: DEX could protect against sepsis-induced intestinal mucosal injury by up-regulating HIF-1ɑ expression in rats.
ABSTRACT
Objective To investigate the relationship between TNF-α, IFN-γand intestinal muco-sal permeability in a mouse colitis model and its inhibiting effect by balsalazide. Methods Forty-five C57BL/6J mice were divided randomly into five groups. Normal group was only fed with distilled water, DSS group and balsalazide groups at doses of 42, 141,423 mg/kg were both fed with 5% DSS. Balsalazide was given by intragastric administration. At the end of the experiment, colon tissue was collected for assessment of histological index(HI) and the MPO activity. Small intestinal mucosa was collected for assessment of the content of TNF-α and IFN-γ,transmission electron microscope(TEM), and detection of permeability by Ev-arts blue method. Results Compared with normal group, DSS group mice all manifested severe weight loss associated with hematocbezia and diarrhea, HI score, and the colon MPO activity and the content of TNF-α and IFN-γ were increased significantly. Intestinal mucosa showed a thinning of microvillous carpet, with de-curtated and broaden junctional complex and enlarged intercollutar space under TEM observations. The amount of Evans blue permeated into intestinal wall was obvious. Compared with DSS group, the HI score, the MPO activity and the content of TNF-α and IFN-γ were decreased by balsalazide. The amount of Evans blue permeated into intestinal wall was less. Ileal microvillous carpet was ameliorated dose dependently by balsalazide. Conclusion In DSS-induced colitis model, the change of the content of the TNF-α and IFN-γ, was accordance with the increase of intestinal mucosal permeability while balsalazide can significantly amelio-rate intestinal mucosal permeability by its anti-colitis effect.