Repeated administration of analgesic-dose S-ketamine alleviates severe burn-induced intestinal injury in mice
Objective To evaluate the effect of repeated analgesic doses of S-ketamine(Esk)on intestinal injury in severely burned mice.Methods Adult male specific pathogen free(SPF)C57BL/6J mice were randomly divided into four groups:sham burn group(Sham group),severe burn model group(Mod group),sham burn+Esk group(Sham+Esk group),and severe burn+Esk group(Mod+Esk group).A 40％total body surface area deep second degree burn model was prepared.The Sham+Esk and Mod+Esk groups received intraperitoneal injections of Esk at a dose of 10 mg/kg.Pain and distress scale,surcrose preference(SP)test,and 8-day survival rate were observed at multiple time points before and after modeling(n=10).Mice were gavaged with fluorescein isothiocyanate-labeled dextran(FITC-dex-tran)at 22 h after modeling(n=4).At 24 h post-modeling,mice were euthanized,and serum was col-lected to compare FITC-dextran concentrations.Meanwhile,intestinal Chiu's injury scores,glycogen(+)cell counts,terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL)apoptosis index,intestine tumor necrosis factor(TNF)-α and interleukin(IL)-1 β levels,and intestinal tight junction pro-teins(Claudin7 and ZO-1)levels were measured(n=6).Multiple group comparisons at the same time points were performed using one-way analysis of variance or non-parametric tests,and comparisons between two groups were conducted using t-tests or Mann-Whitney tests.Results The apoptosis index of the small intestine mucosa in Mod group was higher than that in Sham group[(28.3±7.2)％vs.(3.1±2.3)％,t=12.82,P＜0.01],and the serum FITC-dextran concentration was higher than that in Sham group[(0.66±0.01)vs.(0.60±0.01)mg/ml,t=11.63,P＜0.01];The average number of glycogen(+)cells in a single intestinal villus was less in the Mod group(7.3±3.0 vs.29.1±5.5,t=5.78,P＜0.01),and the relative intensity of ZO-1 protein was lower than in the Sham group(0.3±0.2 vs.1.2± 0.1,t=5.53,P＜0.01).After Esk treatment,the intestinal apoptosis index in the Mod+Esk group de-creased compared to the Mod group[(14.5±4.6)％vs.(28.3±7.2)％,t=12.82,P＜0.01],and the serum FITC-dextran concentration was lower than that in the Mod group[(0.63±0.01)vs.(0.66± 0.01)mg/ml,t=5.768,P＜0.01];The number of glycogen(+)cells and the relative strength of Clau-din 7 protein were higher than those in the Mod group(14.1±3.5 vs.7.3±3.0,t=5.78,P＜0.01;1.3±0.2 vs.0.6±0.4,t=3.07,P＜0.05).Conclusion Analgesic dose of S-ketamine can alleviate severe burn-induced intestinal barrier injury in mice.The mechanism may be associated with promoting in-testinal mucus secretion and improving intestinal inflammation.
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