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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.
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Nowadays, non-alcoholic fatty liver disease (NAFLD) is prevalent all over the world, and its incidence has been increasing year by year in China. The four aspects of intestinal mucosal barrier, including mechanical barrier, chemical barrier, biological barrier and immunological barrier are interrelated closely and related to NAFLD. This article reviewed the influence of intestinal mucosal barrier dysfunction on NAFLD.
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Objective: To prepare and optimize the formulation of intranasal thermo-sensitive gel of Zhi Xiong San and to evaluate its in vitro release mechanism and nasal mucosa permeability. Methods: The formulations of poloxamer thermo-sensitive gel were optimized by a central composite design-response surface method and its in vitro release mechanism and nasal mucosa permeability were evaluated by Franz diffusion chambers. Results: The optimal formulation was Poloxamer 407 (P407) 20% and Poloxamer 188 (P188) 6.5%. Imperatorin was released from the thermo-sensitive gels approximately with a zero-order mechanism, while ferulic acid with a Higuchi model. The formulation demonstrated the enhancement of nasal mucosa permeability. Conclusion: The optimal formulation provides a basis for the development of new administration routes and dosage forms of Zhi Xiong San.
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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.
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PURPOSE: The relative impermeability of the bladder mucosa is due to the glycosaminoglycan layer covering the urothelium and the tight junction of the urothelium. Recently, one of the most popular theories of interstitial cystitis is the penetration of urinary irritants into the suburothelial tissue due to an increased permeability of the urothelium. This study was performed to evaluate the effect of the intravesical heparin treatment on the permeability of bladder mucosa in allergic cystitis. MATERIALS AND METHODS: Rats were sensitized by intraperitoneal injection of ovalbumin(10mg/m1/kg) given on days 1, 3 and 5. The experiments were performed 4 weeks afrer the last injection. Controls were run simultaneously with the sensitized animals. Sensitized rats were challenged with intravesical ovalbumin(10mg/m1, 1ml) and control rats received 1 ml saline Intravesically. Sensitized-antigen challenged group was divided into two subgroups; rats treated with intravesical hepanin(5mg/ml in 0.9% NaCl) or those treated with 1 ml saline intravesically Immediately following the intravesical heparin(or saline) treatment, 1ml of 14C-urea was placed into the bladder for two hours. We examined the peripheral blood concentration of 14C-urea at periods up to 120 minutes. RESULTS: There was no 14C-urea present in the blood in control group. There was a progressive increase in the blood level of 14C-urea with time in the sensitized-antigen challenge group. Compared with intravesical saline treatment group, there was less progressive increase in the blood level of 14C-urea with time in the intravesical heparin treatment group. W8 also measured radioactivity of 14C-urea in the bladder tissues and found significantly lower level of 14C-urea in the bladder tissues from intravesical heparin treatment group than intravesical saline treatment group. CONCLUSIONS: This study indicates that immunologically induced cystitis increases bladder mucosal permeability in rats and intravesical heparin treatment decrease the permeability significantly.