Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to stu...Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S.aureus infection.However,the contribution of HLA DP to S.aureus infection is unknown yet.Methods:In this study,we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes.Neo-floxed IAβ+/-mice were crossbred with Ella-Cre and further crossbred with HLA DP401 or HLA-DRA0101 humanized mice.After several rounds of traditional crossbreeding,we finally obtained HLA DP401-IAβ-/-and HLA DRA-IAβ-/-humanized mice,in which human DP401 or DRA0101 molecule was introduced into IAβ-/-mice deficient in endogenous murine MHC classⅡmolecules.A transnasal infection murine model of S.aureus pneumonia was induced in the humanized mice by administering 2×108CFU of S.aureus Newman dropwise into the nasal cavity.The immune responses and histopathology changes were further assessed in lungs in these infected mice.Results:We evaluated the local and systemic effects of S.aureus delivered intranasally in HLA DP401-IAβ-/-and HLA DRA-IAβ-/-transgenic mice.S.aureus Newman infection significantly increased the m RNA level of IL 12p40 in lungs in humanized mice.An increase in IFN-γand IL-6 protein was observed in HLA DRA-IAβ-/-mice.We observed a declining trend in the percentage of F4/80+macrophages in lungs in HLA DP401-IAβ-/-mice and a decreasing ratio of CD4+to CD8+T cells in lungs in IAβ-/-mice and HLA DP401-IAβ-/-mice.A decreasing ratio of Vβ3+to Vβ8+T cells was also found in the lymph node of IAβ-/-mice and HLA DP401-IAβ-/-mice.S.aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ-/-genetic background mice.Conclusion:These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S.aureus pneumonia and study what role DP molecule plays in S.aureus infection.展开更多
目的:研究补中益气法对甲状腺功能减退(甲减)大鼠心肌肌球蛋白重链α和β(myosin heavy chain alpha and beta,α-MHC和β-MHC)mRNA表达的影响。方法:将甲减Wistar大鼠随机分为模型对照组、L-T4组、补中益气汤组。实时定量RT-PCR法测心...目的:研究补中益气法对甲状腺功能减退(甲减)大鼠心肌肌球蛋白重链α和β(myosin heavy chain alpha and beta,α-MHC和β-MHC)mRNA表达的影响。方法:将甲减Wistar大鼠随机分为模型对照组、L-T4组、补中益气汤组。实时定量RT-PCR法测心肌α-MHC和β-MHC mRNA。结果:给处理因素8周,L-T4组、补中益气汤组的α-MHCmRNA的表达分别为正常组的1.77倍、2.32倍,补中益气汤组较L-T4组上升明显(P<0.05);L-T4组、补中益气汤组β-MHCmRNA的表达分别为正常组的2.61倍、1.17倍,补中益气汤组下调明显(P<0.05)。结论:补中益气法在甲减心肌损伤的修复中起重要作用,其机制与其提高心肌α-MHC mRNA的表达、降低β-MHCmRNA的表达有关。展开更多
基金National Science and Technology Major Project,Grant/Award Number:2016YFD0500208,2017ZX10304402-001-012 and 2017ZX10304402-001-006Shanghai Science and Technology Commission“R&D public service platform and institutional capacity improvement project”,Grant/Award Number:21DZ2291300Shanghai Public Health Clinical Center projects,Grant/Award Number:KY-GW-2021-39,KY-GW-2019-19 and KY-GW-2019-11。
文摘Background:Staphylococcus aureus can cause serious infections by secreting many superantigen exotoxins in“carrier”or“pathogenic”states.HLA DQ and HLA DR humanized mice have been used as a small animal model to study the role of two molecules during S.aureus infection.However,the contribution of HLA DP to S.aureus infection is unknown yet.Methods:In this study,we have produced HLA DP401 and HLA DRA0101 humanized mice by microinjection of C57BL/6J zygotes.Neo-floxed IAβ+/-mice were crossbred with Ella-Cre and further crossbred with HLA DP401 or HLA-DRA0101 humanized mice.After several rounds of traditional crossbreeding,we finally obtained HLA DP401-IAβ-/-and HLA DRA-IAβ-/-humanized mice,in which human DP401 or DRA0101 molecule was introduced into IAβ-/-mice deficient in endogenous murine MHC classⅡmolecules.A transnasal infection murine model of S.aureus pneumonia was induced in the humanized mice by administering 2×108CFU of S.aureus Newman dropwise into the nasal cavity.The immune responses and histopathology changes were further assessed in lungs in these infected mice.Results:We evaluated the local and systemic effects of S.aureus delivered intranasally in HLA DP401-IAβ-/-and HLA DRA-IAβ-/-transgenic mice.S.aureus Newman infection significantly increased the m RNA level of IL 12p40 in lungs in humanized mice.An increase in IFN-γand IL-6 protein was observed in HLA DRA-IAβ-/-mice.We observed a declining trend in the percentage of F4/80+macrophages in lungs in HLA DP401-IAβ-/-mice and a decreasing ratio of CD4+to CD8+T cells in lungs in IAβ-/-mice and HLA DP401-IAβ-/-mice.A decreasing ratio of Vβ3+to Vβ8+T cells was also found in the lymph node of IAβ-/-mice and HLA DP401-IAβ-/-mice.S.aureus Newman infection resulted in a weaker pathological injury in lungs in IAβ-/-genetic background mice.Conclusion:These humanized mice will be an invaluable mouse model to resolve the pathological mechanism of S.aureus pneumonia and study what role DP molecule plays in S.aureus infection.
文摘目的:研究补中益气法对甲状腺功能减退(甲减)大鼠心肌肌球蛋白重链α和β(myosin heavy chain alpha and beta,α-MHC和β-MHC)mRNA表达的影响。方法:将甲减Wistar大鼠随机分为模型对照组、L-T4组、补中益气汤组。实时定量RT-PCR法测心肌α-MHC和β-MHC mRNA。结果:给处理因素8周,L-T4组、补中益气汤组的α-MHCmRNA的表达分别为正常组的1.77倍、2.32倍,补中益气汤组较L-T4组上升明显(P<0.05);L-T4组、补中益气汤组β-MHCmRNA的表达分别为正常组的2.61倍、1.17倍,补中益气汤组下调明显(P<0.05)。结论:补中益气法在甲减心肌损伤的修复中起重要作用,其机制与其提高心肌α-MHC mRNA的表达、降低β-MHCmRNA的表达有关。
