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Objective:To provide experimental evidences for choosing murine models in the pathogenesis research of thymic impairment induced by viral infection,we compared the impacts of polycytidylic acid(Poly(I:C)) and dexamethasone(DEX) on the thymic morphology and thymic output function,and explored the implication of RLR signaling pathway.Methods: 24 male C57BL/6 mice were randomly assigned into three groups and treated with Poly(I:C),DEX,or saline respectively.Thereafter,their thymic morphology,pathological changes,thymic index,and thymic pathology were examined.Their contents of T-cell receptor excision circles (TRECs) and proportions of the naive CD4+T cell in the peripheral blood were determined to evaluate their thymic output function.The expression levels of thymic RLR/MAVS/IFN-α/β signaling pathway and IL-1β were also measured.Results: Both Poly (I:C) and DEX treatment caused thymic atrophy in appearance and structural destruction under the microscope inspection,and DEX treatment did much more severe damage,especially to the thymic cortex.TRECs decreased significantly in both groups.The proportions of na?ve/memory CD4+T cell subsets remained stable,though total CD4+T cell decreased in DEX group,while the proportion of na?ve CD4+T cell in Poly (I:C) group increased significantly.The expression of RIG-Ⅰ,MDA5,LGP2,and IFN-α/β were up-regulated in DEX group, while it remained unchanged in Poly (I:C) group.Conclusion:Both Poly (I:C) and DEX induced thymic atrophy and the impaired thymic output function.Nevertheless,the expression of RLR-IFN signaling pathway up-regulated more significantly in DEX group instead of in Poly (I:C) group.These results implied the existence of different pathological manifestations and mechanisms underlying the impaired thymic function in different animal models,as well as impact on na?ve/memory CD4+T cell proportions.Our research provides references for choosing animal models in the basic research and drug development for viral infection induced thymic atrophy based on the RLR signaling pathway.
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Objective To study the foxml gene and its protective effect on the lung tissue of rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS), and to observe the dexamethason' s (DEX) impacts on foxml gene and the prognosis of ALI. Method Seventy-two healthy mice were randomly(random number) divid-ed into three groups: control group (A group, n = 24), model group (B group, n = 24) and DEX treatment group (C group, n = 24). The observing intervals were respectively set in 24 h, 48 h and 72 hours. At each ob-serving interval, the foxml protein in lung tissue of mice was detected by using immunohistochemistry (IHC), and the expression of foxml gene in lung tissue was detected by using RT-PCR, as well as to observe the pathological changes in lung tissue. Results Comparisons were made between paired groups at 24 h,48 h and 72 h intervals in which the expression of foxml mRNA and the level of foxml protein in lung tissue of mice in C group were signifi-cantly higher than those in B group (P < 0.05), and those in B group were significantly higher than those in A group (P < 0.05). The expression of foxml mRNA and the level of foxml protein in lung tissue of mice in B group at 48 h interval were significantly higher than those both at intervals of 72 h and 24 h (P < 0.05), and the those at 72 interval were significantly higher than those at 24 h interval (P < 0.05). Compared with B group, the pathologi-cal changes in lung tissue of mice in C group were lessened. Conclusions In both model group and dexamethasone treatment group, the expression of foxml mRNA and the level of foxml protein in lung tissue of mice are increased significantly. Dexamethasone lessens the injury of both vascular endothelial cells and alveolar epithelial ceils of lung tissue, and it also significantly increases the expression of foxml mRNA and the level of foxml protein.
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Objective To compare the efficacies of intralesional hyaluronidase(HAase), intralesional dexamethasone(DEX), and intralesional HAase plus intralesional DEX on skin damage caused by vinorelbine extravasation in a rat model. Methods After establishing an animal model with vinorelbine extravasation in each lower extremity of 40 Sprague-Dawley rats, we treated the rats with intralesional HAase,intralesional DEX, intralesional HAase plus intralesional DEX,intralesional saline,or received no treatment as control.The wound area on 1 d, 4 d, 8 d, 12 d, 18 d, 24 d, 30 d and the time of healing were observed and compared.Results The wound area on 1 d, 4 d, 8 d, 12 d, 18 d and 24 d was significantly lower in intralesional HAase group, intralesional DEX group,intralesional HAase plus intralesional DEX group,and intralesional saline group than that in control group (P ＜0.05), and that was significantly lower in intralesional HAase group and intralesional HAase plus intralesional DEX group than that in intralesional DEX group and intralesional saline group (P ＜0.05). The healing time was significantly shorter in 4 therapy groups than that in control group [(25.1±3.1) d, (27.9±2.8) d, (23.0±3.2) d, and (28.4±3.9) d vs.(31.2±3.0) d, P ＜0.05], and that was significantly lower in intralesional HAase group and intralesional HAase plus intralesional DEX group than that in intralesional DEX group and intralesional saline group (P ＜0.05). Conclusion The monotherapy with intralesional HAase or intralesional DEX, with decreasing the extent of skin damage and shortening the healing time, is effective therapy for skin damage caused by vinorelbine extravasation, and the monotherapy with intralesional Haase is more efficacious. The efficacy of intralesional HAase plus intralesional DEX seems better than that of monotherapy.
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Objective: To study the effect of astragaloside (AST) on the injury induced by amyloid β-protein (Aβ) plus Dexamethasone (DEX) in rat hippocampal neurons. Methods: In vitro, the effects of AST on hippocampal neurons cell death with Aβ plus DEX were detected by MTT assay and intracellular calcium ([Ca2+]i); The effects of AST on phospho-tau (P-tau) protein were analyzed to explore the mechanisms responsible for DEX enhanced Aβ-induced cell death in hippocampal neurons. Results: AST (10, 20, and 40 μg/mL) could protect hippocampal neurons against DEX (10 μmol/L) plus Aβ25-35 (5 μmol/L) - induced hippocampal neuronal injury of felal rat in vitro (P<0.01). AST could inhibit the increased levels of [Ca2+]i and P-tau protein level induced by DEX (10 μmol/L) plus Aβ25-35 (5 μmol/L) (P < 0.05). Conclusion: AST could protect hippocampal neuron against synergistic neurotoxicity of Aβ and DEX.
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